Strain Name:

FVB.C-Npc1m1N/J

Stock Number:

021755

Order this mouse

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
This knockout allele of the Npc1 (Niemann Pick type C1) gene may be useful in studies of Niemann-Pick Type C disease.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating InvestigatorDr. Matthew Scott,   Stanford University School of Medicine

Description
This FVB/NJ congenic model of Niemann-Pick Type C disease was derived from backcrosses of the original Npc1m1N (Niemann Pick type C1 NIH) spontaneous mutation strain (see Stock No. 003092).

Homozygous mice show reduced levels of myelin in the cerebellum. Astrocytes and microglia proliferate and occupy areas of neuronal loss or degeneration. Weight loss is accompanied by a progressive motor coordination deficit, or ataxia, at least as early as postnatal day 45 (P45). The lifespan of homozygous animals is reduced to a mean of 76 days.

Rescue of NPC1 deficiency can be achieved in a tissue-specific manner through crosses with a tetracycline-inducible tetO-Npc1-YFP transgenic animal (see Stock No. 021065) and an appropriate tTA/rtTA tetracycline-responsive mutant line.

Development
824 bp of MaLR retroposon-like DNA replaced 703 bp of wild-type genomic sequence spanning 44 bp of an exon and 659 bp of the downstream intron. The insertion results in premature truncation of the protein deleting 11 out of 13 transmembrane domains. Northern blot analysis revealed marked decrease in gene expression in liver and brain from homozygous mutant animals. This mutation arose spontaneously on the BALB/cNctr inbred background (see Stock No. 003092) and was backcrossed to FVB/NJ for more than 10 generations by the donating laboratory to create a congenic line.

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Npc1m1N allele
003092   BALB/cNctr-Npc1m1N/J
View Strains carrying   Npc1m1N     (1 strain)

Strains carrying other alleles of Npc1
004817   C57BL/6J-Npc1nmf164/J
002760   C57BLKS/J-Npc1spm/J
021065   FVB(C)-Tg(tetO-Npc1/YFP)1Mps/J
View Strains carrying other alleles of Npc1     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Niemann-Pick Disease, Type C1; NPC1
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Npc1m1N/Npc1m1N

        involves: BALB/c
  • mortality/aging
  • premature death
    • ~75 day life span   (MGI Ref ID J:81305)
    • mice die between 80 and 100 days of age from neurodegenerative disease   (MGI Ref ID J:130969)
  • behavior/neurological phenotype
  • abnormal motor capabilities/coordination/movement
    • defects beginning at 7 to 8 weeks of age   (MGI Ref ID J:76733)
    • impaired coordination
      • mice exhibit impaired coordination around 40 days of age with coordination worsening as the mice age   (MGI Ref ID J:130969)
  • decreased food intake
    • poor food intake, beginning at 7 weeks of age   (MGI Ref ID J:76733)
  • growth/size/body phenotype
  • decreased body size
    • female homozygotes display a smaller stature than wild-type females   (MGI Ref ID J:91430)
    • decreased body weight   (MGI Ref ID J:204311)
      • female homozygotes display a reduced body mass relative to wild-type females   (MGI Ref ID J:91430)
      • weight loss
        • beginning at 7 to 8 weeks of age   (MGI Ref ID J:76733)
        • mice exhibit weight loss starting at 40 days of age   (MGI Ref ID J:130969)
  • hematopoietic system phenotype
  • abnormal alveolar macrophage morphology
    • alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials   (MGI Ref ID J:204311)
    • alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 6-fold and cholesterol levels are elevated 15-fold in alveolar macrophages   (MGI Ref ID J:204311)
  • enlarged spleen
    • progressive splenomegaly, beginning at 7 weeks of age   (MGI Ref ID J:76733)
  • homeostasis/metabolism phenotype
  • abnormal cellular cholesterol metabolism
    • higher rate of turnover although whole body pool is considerably elevated   (MGI Ref ID J:104996)
    • rate of cholesterol synthesis is reduced   (MGI Ref ID J:104996)
  • abnormal lipid level
    • elevation in lipid content in the lungs   (MGI Ref ID J:204311)
    • abnormal phospholipid level
      • increase in phospholipid content in the lungs   (MGI Ref ID J:204311)
      • 4-fold elevation of phospholipid levels of bronchoalveolar lavage   (MGI Ref ID J:204311)
      • 2- to 2.8-fold increase in phospholipid levels in lamellar bodies   (MGI Ref ID J:204311)
      • increase in surfactant phospholipid levels   (MGI Ref ID J:204311)
    • decreased brain cholesterol level
      • decreased levels in the brain at 7 weeks of age relative to controls   (MGI Ref ID J:104996)
      • mice have decreased levels of total cholesterol in the brain   (MGI Ref ID J:130969)
    • increased cholesterol level
      • elevated in most organs except the brain at 7 weeks of age   (MGI Ref ID J:104996)
      • elevated in the brain at 1 day of age   (MGI Ref ID J:104996)
      • mice have increased cholesterol levels in the liver, spleen, intestine and lung   (MGI Ref ID J:130969)
      • increase in cholesterol content in the lungs   (MGI Ref ID J:204311)
      • 12-fold elevation of cholesterol levels in branchoalveolar lavage   (MGI Ref ID J:204311)
      • 6.8-fold increase in cholesterol levels in lamellar bodies   (MGI Ref ID J:204311)
      • increased circulating cholesterol level
        • progressively increasing plasma cholesterol levels   (MGI Ref ID J:18511)
    • lipidosis
      • lipid accumulation (including sphingomyelin, glucocerebroside, lactosylceramide, and cholesterol) in various organs including the liver, lung, kidney, thymus, spleen, and brain   (MGI Ref ID J:18511)
      • at 7-8 weeks of age, female homozygotes show lipid accumulation in mural granulosa cells and in the ovarian stroma, as shown by oil-red-O staining   (MGI Ref ID J:91430)
      • lungs exhibit surfactant accumulation, indicating alveolar lipidosis   (MGI Ref ID J:204311)
  • decreased prolactin level
    • mutant pituitaries exhibit decreased concentrations of prolactin, consistent with a significant reduction in pituitary prolactin mRNA   (MGI Ref ID J:91430)
    • however, chronic (4-week) treatment with 17beta-estradiol (E2) dramatically increases the cytoplasmic signal for prolactin, well in excess of that found in wild-type pituitaries   (MGI Ref ID J:91430)
    • decreased circulating prolactin level
      • female homozygotes show a dramatic reduction in serum prolactin levels relative to wild-type controls   (MGI Ref ID J:91430)
  • increased circulating follicle stimulating hormone level
    • female homozygotes show a 25% increase in serum FSH levels relative to wild-type controls   (MGI Ref ID J:91430)
  • increased circulating luteinizing hormone level
    • female homozygotes show a dramatic increase in serum LH levels relative to wild-type controls   (MGI Ref ID J:91430)
    • in contrast, pituitary expression and circulating levels of GH remain unaffected   (MGI Ref ID J:91430)
  • pulmonary alveolar proteinosis
    • proteinaceous-like material in the alveolar space   (MGI Ref ID J:204311)
    • mild protein accumulation in bronchoalveolar lavage   (MGI Ref ID J:204311)
  • immune system phenotype
  • abnormal alveolar macrophage morphology
    • alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials   (MGI Ref ID J:204311)
    • alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 6-fold and cholesterol levels are elevated 15-fold in alveolar macrophages   (MGI Ref ID J:204311)
  • enlarged spleen
    • progressive splenomegaly, beginning at 7 weeks of age   (MGI Ref ID J:76733)
  • liver/biliary system phenotype
  • enlarged liver
    • hepatomegaly and associated pale liver, presumably due to lipid accumulation   (MGI Ref ID J:91430)
    • increased liver weight
      • progressive increase in liver weight, beginning at 7 weeks of age   (MGI Ref ID J:76733)
  • hepatic steatosis
    • massive liver storage of cholesterol in mice on a high fat, 1% cholesterol diet   (MGI Ref ID J:100351)
  • pale liver   (MGI Ref ID J:91430)
  • reproductive system phenotype
  • abnormal female reproductive system morphology
    • at 7-8 weeks of age, female homozygotes exhibit a thinner reproductive tract than wild-type females   (MGI Ref ID J:91430)
    • abnormal ovary morphology
      • at 7-8 weeks of age, the stromata of mutant ovaries contain numerous islands of foamy cells composed of healthy nuclei and vacuolated cytoplasm   (MGI Ref ID J:91430)
      • these cell nests are replete with lipid, as shown by oil-red-O staining   (MGI Ref ID J:91430)
      • abnormal ovarian follicle morphology
        • at 7 weeks of age, mutant ovarian follicles and stromata exhibit lipid accumulation, as shown by oil-red-O staining   (MGI Ref ID J:91430)
        • abnormal granulosa cell morphology
          • at 7-8 weeks of age, mutant mural granulosa cells exhibit lipid accumulation, as shown by oil-red-O staining   (MGI Ref ID J:91430)
        • abnormal secondary ovarian follicle morphology
          • at 7 weeks of age, mutant antral follicles are smaller than the largest follicles found in wild-type controls   (MGI Ref ID J:91430)
          • the number of mutant secondary and antral follicles is reduced relative to wild-type controls   (MGI Ref ID J:91430)
          • exogenous gonadotropin treatment induces development of numerous large antral follicles at 48 hrs in both wild-type and mutant ovaries; however, mutant ovaries display fewer large follicles in response to eCG   (MGI Ref ID J:91430)
          • chronic treatment of 8-wk-old female mutants with 17beta-estradiol (E2) increases the number of secondary and large antral follicles, well in excess of that found in untreated mutant ovaries   (MGI Ref ID J:91430)
        • absent mature ovarian follicles
          • mutant ovarian follicles fail to mature to the large antral and preovulatory stages   (MGI Ref ID J:91430)
      • absent corpus luteum
        • at 7-8 weeks of age, no formation of corpora lutea is observed   (MGI Ref ID J:91430)
        • injection of hCG after eCG treatment induces formation of corpora lutea in both wild-type and mutant mice; however, less than half the number of corpora lutea are detected in mutant ovaries   (MGI Ref ID J:91430)
      • small ovary
        • at 7-8 weeks, but not at 3 weeks, of age mutant ovaries are smaller than wild-type   (MGI Ref ID J:91430)
        • decreased ovary weight
          • at 7-8 weeks of age, the average weight of mutant ovaries is 1.1 +/- 0.22 mg vs 4.76 +/- 0.51 mg for wild-type ovaries   (MGI Ref ID J:91430)
    • decreased endometrial gland number
      • at 7-8 weeks of age, reduction in the endometrial stroma is associated with a reduction in the convolution of uterine glands   (MGI Ref ID J:91430)
    • endometrium atrophy   (MGI Ref ID J:91430)
    • thin endometrium
      • at 8 weeks of age, a reduction in endometrial thickness is observed   (MGI Ref ID J:91430)
    • thin myometrium   (MGI Ref ID J:91430)
    • thin uterus
      • at 7-8 weeks of age, mutant uteri are thinner than wild-type   (MGI Ref ID J:91430)
    • uterus atrophy
      • at 7-8 weeks of age, atrophy of the myometrium, endometrial stroma, and the endometrial epithelium is observed   (MGI Ref ID J:91430)
  • abnormal ovarian secretion
    • adult mutant ovaries show near absence of 17beta-estradiol (E2) content (2.0 pg) relative to 110-135 pg/ovary in wild-type controls   (MGI Ref ID J:91430)
    • expression of two key steroidogenic proteins (StAR and Cyp19) is markedly reduced in mutant ovaries relative to wild-type controls   (MGI Ref ID J:91430)
    • however, exogenous gonadotropin treatment restores expression of both steroidogenic proteins to wild-type levels   (MGI Ref ID J:91430)
  • absent estrous cycle
    • female homozygotes are acyclic   (MGI Ref ID J:91430)
  • anovulation
    • at 7-8 weeks of age, mutant ovaries display no evidence of ovulation   (MGI Ref ID J:91430)
    • exogenous gonadotropin treatment induces ovulation in both wild-type and mutant ovaries; however, mutant ovaries exhibit fewer large follicles in response to eCG and fewer ovulations in response hCG   (MGI Ref ID J:91430)
    • mutant ovaries transplanted under wild-type kidney capsules display evidence of ovulation, as shown by the presence of corpora lutea and an extraovarian oocyte   (MGI Ref ID J:91430)
  • arrest of spermatogenesis
    • male homozygotes show a partial arrest of spermatogenesis, with some tubules containing fused spermatogenic cells with more than one nucleus while other tubules appear normal   (MGI Ref ID J:119302)
  • impaired acrosome reaction
    • in vitro, mutant sperm are able to bind to zona-free eggs as well as wild-type sperm but fail to fuse with the egg plasma membrane   (MGI Ref ID J:119302)
    • when zona-intact eggs are used, the in vitro capacity of mutant sperm to bind to the egg zona pellucida is only 14% of the level in wild-type sperm   (MGI Ref ID J:119302)
    • interestingly, 30% of total cyritestin protein is not proteolytically processed on mutant cauda sperm, whereas fertilin beta is processed normally   (MGI Ref ID J:119302)
  • impaired fertilization
    • in vitro, mutant sperm are unable to fertilize cumulus-intact eggs (CIE) and produce two-cell embryos, unlike wild-type sperm which fertilize ~56% of CIE   (MGI Ref ID J:119302)
  • infertility
    • females showed normal oogenesis, but lacked implantation sites after successful plugging   (MGI Ref ID J:76395)
    • female infertility
      • female homozygotes are infertile   (MGI Ref ID J:91430)
    • male infertility
      • male homozygotes are infertile   (MGI Ref ID J:119302)
  • oligozoospermia
    • at 60 days of age, the total number of mutant cauda sperm is reduced to only ~28% of that in wild-type males   (MGI Ref ID J:119302)
  • seminiferous tubule degeneration
    • some mutant seminiferous tubules exhibit evidence of extensive degeneration   (MGI Ref ID J:119302)
  • teratozoospermia
    • at 60 days of age, male homozygotes show a significantly higher frequency of abnormal cauda sperm morphology than wild-type males (~32% vs ~7%, respectively)   (MGI Ref ID J:119302)
    • abnormal sperm head morphology
      • at 60 days of age, aberrant cauda sperm heads are frequentyly observed   (MGI Ref ID J:119302)
      • absent sperm head
        • at 60 days of age, headless sperm tails are frequently observed   (MGI Ref ID J:119302)
    • absent sperm flagellum
      • at 60 days of age, tailless sperm heads are frequently observed   (MGI Ref ID J:119302)
  • respiratory system phenotype
  • abnormal lung morphology
    • lungs contain 'nests' of vacuolar filled macrophages and enlarged foamy alveolar macrophages   (MGI Ref ID J:204311)
    • abnormal alveolar macrophage morphology
      • alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials   (MGI Ref ID J:204311)
      • alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 6-fold and cholesterol levels are elevated 15-fold in alveolar macrophages   (MGI Ref ID J:204311)
    • abnormal lung vasculature morphology
      • capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in the lungs   (MGI Ref ID J:204311)
      • enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries   (MGI Ref ID J:204311)
    • abnormal type II pneumocyte morphology
      • alveolar type II cells have many autophagosomes   (MGI Ref ID J:204311)
      • abnormal alveolar lamellar body morphology
        • cholesterol and phospholipid accumulation in lamellar bodies of alveolar type II cells   (MGI Ref ID J:204311)
        • enlarged alveolar lamellar bodies
          • 42% of alveolar type II cell lamellar bodies are enlarged compared to 15% in wild-type mice   (MGI Ref ID J:204311)
    • increased lung weight
      • progressive increase in lung weight, beginning at 7 weeks of age   (MGI Ref ID J:76733)
      • lung weight as a % of total body weight is higher   (MGI Ref ID J:204311)
    • pulmonary alveolar proteinosis
      • proteinaceous-like material in the alveolar space   (MGI Ref ID J:204311)
      • mild protein accumulation in bronchoalveolar lavage   (MGI Ref ID J:204311)
    • thick pulmonary interalveolar septum
      • thickening of the intra-alveolar septae with a slight enlargement of the airways   (MGI Ref ID J:204311)
  • abnormal respiratory system physiology
    • liposome degradation is reduced by 46% in the lungs   (MGI Ref ID J:204311)
    • abnormal surfactant composition
      • increase in surfactant phospholipid levels   (MGI Ref ID J:204311)
  • nervous system phenotype
  • abnormal CNS glial cell morphology
    • glial cells in the corpus callosum reduced by 52%   (MGI Ref ID J:126474)
  • abnormal adenohypophysis morphology
    • the mutant anterior pituitary displays vacuolated cells, suggestiing low rates of feedback control and increased hormone synthesis and secretion   (MGI Ref ID J:91430)
    • adenohypophysis hypoplasia
      • the mutant anterior pituitary is hypoplastic relative to wild-type   (MGI Ref ID J:91430)
    • decreased lactotroph cell number
      • the mutant anterior pituitary shows a dramatic reduction in acidophil cell number relative to wild-type   (MGI Ref ID J:91430)
      • however, chronic (4-week) treatment with 17beta-estradiol (E2) restores pituitary volume and acidophil numbers to wild-type levels   (MGI Ref ID J:91430)
  • abnormal cerebellum anterior vermis morphology
    • by P45, Purkinje cell loss was most evident in the anterior cerebellar vermis   (MGI Ref ID J:81305)
    • degenerating cells belonged preferentially to the zebrin II-negative subtype   (MGI Ref ID J:81305)
  • abnormal cerebellum posterior vermis morphology
    • by P45, some Purkinje cell loss was evident in the posterior cerebellar vermis   (MGI Ref ID J:81305)
    • at P60, most surviving Purkinje cells were located in the posterior vermis   (MGI Ref ID J:81305)
  • abnormal myelination
    • reduced levels of both myelin protein and myelin cholesterol   (MGI Ref ID J:104996)
  • abnormal neuron morphology
    • vacuolated cytoplasmic storage material in all regions of the central nervous system   (MGI Ref ID J:104996)
    • abnormal Purkinje cell morphology
      • axonal swelling by 11 weeks of age   (MGI Ref ID J:126474)
      • Purkinje cell degeneration
        • localized axonal swellings, malformations of the dendritic arbor, and accumulation of vesicular storage materials within the cytoplasm   (MGI Ref ID J:81305)
      • decreased Purkinje cell number
        • earliest cell loss at P45 throughout the cerebellum; cell loss was profound by P60 in the anterior lobe of the cerebellum; no marked loss after P75   (MGI Ref ID J:81305)
        • small reduction in Purkinje cell numbers in the cerebellar hemispheres at 3 weeks of age   (MGI Ref ID J:126474)
        • reduction in numbers increases with age   (MGI Ref ID J:126474)
  • decreased brain cholesterol level
    • decreased levels in the brain at 7 weeks of age relative to controls   (MGI Ref ID J:104996)
    • mice have decreased levels of total cholesterol in the brain   (MGI Ref ID J:130969)
  • decreased brain weight
    • progressive decrease in brain weight, beginning at 7 weeks of age   (MGI Ref ID J:76733)
    • brain weight is lower than in controls mice   (MGI Ref ID J:130969)
  • decreased corpus callosum size
    • reduced in size by 50% at 11 weeks of age   (MGI Ref ID J:126474)
    • glial cells reduced by 52%   (MGI Ref ID J:126474)
  • small cerebellum
    • cerebellum weight is smaller than controls   (MGI Ref ID J:130969)
  • cellular phenotype
  • abnormal cellular cholesterol metabolism
    • higher rate of turnover although whole body pool is considerably elevated   (MGI Ref ID J:104996)
    • rate of cholesterol synthesis is reduced   (MGI Ref ID J:104996)
  • absent sperm flagellum
    • at 60 days of age, tailless sperm heads are frequently observed   (MGI Ref ID J:119302)
  • impaired acrosome reaction
    • in vitro, mutant sperm are able to bind to zona-free eggs as well as wild-type sperm but fail to fuse with the egg plasma membrane   (MGI Ref ID J:119302)
    • when zona-intact eggs are used, the in vitro capacity of mutant sperm to bind to the egg zona pellucida is only 14% of the level in wild-type sperm   (MGI Ref ID J:119302)
    • interestingly, 30% of total cyritestin protein is not proteolytically processed on mutant cauda sperm, whereas fertilin beta is processed normally   (MGI Ref ID J:119302)
  • adipose tissue phenotype
  • decreased abdominal fat pad weight
    • female homozygotes exhibit reduced abdominal fat deposits relative to wild-type females   (MGI Ref ID J:91430)
  • endocrine/exocrine gland phenotype
  • abnormal adenohypophysis morphology
    • the mutant anterior pituitary displays vacuolated cells, suggestiing low rates of feedback control and increased hormone synthesis and secretion   (MGI Ref ID J:91430)
    • adenohypophysis hypoplasia
      • the mutant anterior pituitary is hypoplastic relative to wild-type   (MGI Ref ID J:91430)
    • decreased lactotroph cell number
      • the mutant anterior pituitary shows a dramatic reduction in acidophil cell number relative to wild-type   (MGI Ref ID J:91430)
      • however, chronic (4-week) treatment with 17beta-estradiol (E2) restores pituitary volume and acidophil numbers to wild-type levels   (MGI Ref ID J:91430)
  • abnormal ovarian secretion
    • adult mutant ovaries show near absence of 17beta-estradiol (E2) content (2.0 pg) relative to 110-135 pg/ovary in wild-type controls   (MGI Ref ID J:91430)
    • expression of two key steroidogenic proteins (StAR and Cyp19) is markedly reduced in mutant ovaries relative to wild-type controls   (MGI Ref ID J:91430)
    • however, exogenous gonadotropin treatment restores expression of both steroidogenic proteins to wild-type levels   (MGI Ref ID J:91430)
  • abnormal ovary morphology
    • at 7-8 weeks of age, the stromata of mutant ovaries contain numerous islands of foamy cells composed of healthy nuclei and vacuolated cytoplasm   (MGI Ref ID J:91430)
    • these cell nests are replete with lipid, as shown by oil-red-O staining   (MGI Ref ID J:91430)
    • abnormal ovarian follicle morphology
      • at 7 weeks of age, mutant ovarian follicles and stromata exhibit lipid accumulation, as shown by oil-red-O staining   (MGI Ref ID J:91430)
      • abnormal granulosa cell morphology
        • at 7-8 weeks of age, mutant mural granulosa cells exhibit lipid accumulation, as shown by oil-red-O staining   (MGI Ref ID J:91430)
      • abnormal secondary ovarian follicle morphology
        • at 7 weeks of age, mutant antral follicles are smaller than the largest follicles found in wild-type controls   (MGI Ref ID J:91430)
        • the number of mutant secondary and antral follicles is reduced relative to wild-type controls   (MGI Ref ID J:91430)
        • exogenous gonadotropin treatment induces development of numerous large antral follicles at 48 hrs in both wild-type and mutant ovaries; however, mutant ovaries display fewer large follicles in response to eCG   (MGI Ref ID J:91430)
        • chronic treatment of 8-wk-old female mutants with 17beta-estradiol (E2) increases the number of secondary and large antral follicles, well in excess of that found in untreated mutant ovaries   (MGI Ref ID J:91430)
      • absent mature ovarian follicles
        • mutant ovarian follicles fail to mature to the large antral and preovulatory stages   (MGI Ref ID J:91430)
    • absent corpus luteum
      • at 7-8 weeks of age, no formation of corpora lutea is observed   (MGI Ref ID J:91430)
      • injection of hCG after eCG treatment induces formation of corpora lutea in both wild-type and mutant mice; however, less than half the number of corpora lutea are detected in mutant ovaries   (MGI Ref ID J:91430)
    • small ovary
      • at 7-8 weeks, but not at 3 weeks, of age mutant ovaries are smaller than wild-type   (MGI Ref ID J:91430)
      • decreased ovary weight
        • at 7-8 weeks of age, the average weight of mutant ovaries is 1.1 +/- 0.22 mg vs 4.76 +/- 0.51 mg for wild-type ovaries   (MGI Ref ID J:91430)
  • seminiferous tubule degeneration
    • some mutant seminiferous tubules exhibit evidence of extensive degeneration   (MGI Ref ID J:119302)
  • cardiovascular system phenotype
  • abnormal lung vasculature morphology
    • capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in the lungs   (MGI Ref ID J:204311)
    • enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries   (MGI Ref ID J:204311)

Npc1m1N/Npc1m1N

        involves: 129S1/Sv * BALB/c * C57BL/6
  • mortality/aging
  • premature death
    • all mice on a genetic background involving 129S1/Sv, C57BL/6, and BALB/c died by ~120 days of age   (MGI Ref ID J:89617)
  • growth/size/body phenotype
  • weight loss
    • earlier onset and faster progression than in Npc2tm1Plob homozygotes   (MGI Ref ID J:89617)
  • homeostasis/metabolism phenotype
  • abnormal lipid homeostasis
    • cholesterol and other lipid accumulation in the liver at 50 days of age with an ~17 fold increase in plant sterols and marked elevations of sphingomyelin, lyso(bis)phosphatidic acid, gangliosides GM2 and GM3, glucosylceramide, lactosylceramide, and asialo-GM2   (MGI Ref ID J:89617)
    • lipid accumulation in the brain at 50 days was largely limited to glycolipids with 11 to 15 fold increases in glucosylceramide, lactosylceramide, and asialo-GM2   (MGI Ref ID J:89617)
    • galactosylceramide levels were reduced in the brain, reflecting a general loss of myelin lipids   (MGI Ref ID J:89617)
    • increased liver cholesterol level
      • about a 6 fold increase in total cholesterol accumulation in the liver at 28 days of age   (MGI Ref ID J:89617)
      • about a 10 fold increase in total cholesterol accumulation in the liver at 50 days of age   (MGI Ref ID J:89617)
      • no increase in overall cholesterol levels in the brain, putatively due to compensatory losses due to demyelination, neuronal death, and possible imbalance between neuronal cell bodies and distal axons   (MGI Ref ID J:89617)
      • on the cellular level in the brain, unesterified cholesterol was stored in neurons within the neocortex, dentate gyrus, hippocampus, and cerebellum   (MGI Ref ID J:89617)
  • nervous system phenotype
  • Purkinje cell degeneration   (MGI Ref ID J:89617)
  • liver/biliary system phenotype
  • increased liver cholesterol level
    • about a 6 fold increase in total cholesterol accumulation in the liver at 28 days of age   (MGI Ref ID J:89617)
    • about a 10 fold increase in total cholesterol accumulation in the liver at 50 days of age   (MGI Ref ID J:89617)
    • no increase in overall cholesterol levels in the brain, putatively due to compensatory losses due to demyelination, neuronal death, and possible imbalance between neuronal cell bodies and distal axons   (MGI Ref ID J:89617)
    • on the cellular level in the brain, unesterified cholesterol was stored in neurons within the neocortex, dentate gyrus, hippocampus, and cerebellum   (MGI Ref ID J:89617)

Npc1m1N/Npc1m1N

        involves: 129S2/SvPas * BALB/c * C57BL/6
  • mortality/aging
  • premature death
    • lifespan of Npc1-null mice expressing Il6 is modestly reduced compared to double null littermates   (MGI Ref ID J:118352)

Npc1m1N/Npc1m1N

        BALB/cNctr-Npc1m1N/J
  • nervous system phenotype
  • *normal* nervous system phenotype
    • unlike human Niemann-Pick Type C, neurofibrillary tangles are not found in the brain   (MGI Ref ID J:149812)
    • abnormal cerebral cortex morphology
      • accumulation of intracellular free cholesterol results in swollen neurons scattered throughout all neocortical layers; by 3 weeks of age, when clinical symptoms have not presented, there is accumulation of filipin staining in almost all neurons of the central cortex areas, cholesterol storage continues to increase, and by 10 weeks of age neuronal degeneration is found in the retrospinal cortex   (MGI Ref ID J:149812)
      • abnormal neocortex morphology   (MGI Ref ID J:149812)
    • abnormal hippocampus CA3 region morphology
      • although CA1 does not have intracellular free cholesterol accumulation, by 3 weeks of age there is filipin staining material in almost every pyramidal neuron in CA3 and this increases at 5 and 10 weeks of age with extensive degeneration of CA3 neurons by 10 weeks of age   (MGI Ref ID J:149812)
    • abnormal olfactory bulb morphology
      • the olfactory bulb shows increased expression of galectin-3, particularly in the glomerular cell layer, indicating increased inflammatory processes   (MGI Ref ID J:209834)
    • abnormal olfactory nerve morphology
      • the continuity of the olfactory nerve layer is disturbed   (MGI Ref ID J:209834)
      • the olfactory nerve layer shows a disrupted organization of staining for a maker of mature olfactory cells (olfactory marker protein)   (MGI Ref ID J:209834)
    • abnormal olfactory sensory neuron morphology
      • architecture of olfactory receptor neurons is disturbed, showing enlarged gap-like spaces in the basal and middle portions of the epithelium   (MGI Ref ID J:209834)
    • abnormal pons morphology
      • free cholesterol storage in neurons is found throughout the gigantocellular nucleus of the pons, but there is reduced cholesterol staining in the myelin sheaths of surrounding myelinated nerve fibers   (MGI Ref ID J:149812)
    • abnormal trigeminal ganglion morphology
      • myelin-like deposits in trigeminal ganglion cells and satellite cells   (MGI Ref ID J:209834)
    • astrocytosis
      • astrocytosis in the olfactory bulb, particularly within the glomerular layer   (MGI Ref ID J:209834)
    • decreased brain weight
      • decrease in brain weight of old mice   (MGI Ref ID J:209834)
    • decreased prepulse inhibition
      • prepulse inhibition is blunted (45-55%) when compared to wild-type (60-65%)   (MGI Ref ID J:179744)
    • demyelination
      • demyelination is observed in the corpus callosum, external capsule and internal capsule   (MGI Ref ID J:179744)
    • microgliosis
      • microgliosis is seen in the olfactory epithelium and olfactory bulb   (MGI Ref ID J:209834)
      • massive glia activation in the interface between axons of incoming olfactory receptor neurons and mitral cells/periglomerular cells in the olfactory bulb without neuronal loss in this area   (MGI Ref ID J:209834)
    • neurodegeneration
      • peripheral and central neurodgeneration in the olfactory system   (MGI Ref ID J:209834)
      • Purkinje cell degeneration
        • nearly all of the Purkinje cells are lost by 9 to 10 weeks of age   (MGI Ref ID J:149812)
        • pronounced loss of cerebellar Purkinje cells beginning at 6 weeks of age   (MGI Ref ID J:179744)
  • cellular phenotype
  • abnormal cellular cholesterol metabolism   (MGI Ref ID J:149812)
  • abnormal lysosome physiology
    • marker analysis indicates an increase in lysosomal activity and lipid efflux   (MGI Ref ID J:209834)
  • homeostasis/metabolism phenotype
  • abnormal cellular cholesterol metabolism   (MGI Ref ID J:149812)
  • abnormal lipid level
    • GM2 levels are very high in the brain by 15 days of age and remain elevated   (MGI Ref ID J:179744)
    • GM3 levels begin to increase by 15 days of age and rise progressively until at least 90 days   (MGI Ref ID J:179744)
    • decreased liver cholesterol level
      • esterified cholesterol in liver tissue decreases with age   (MGI Ref ID J:179744)
    • increased liver cholesterol level
      • unesterified cholesterol in liver tissue increases with age   (MGI Ref ID J:179744)
  • behavior/neurological phenotype
  • ataxia
    • first observed as a lateral displacement of each rear foot at 7 weeks of age   (MGI Ref ID J:179744)
  • decreased grip strength
    • first observed at 9 weeks of age   (MGI Ref ID J:179744)
  • impaired coordination
    • decrease in motor capabilities as assessed by the inverted cage lid, coat hanger and balance beam tests   (MGI Ref ID J:179744)
  • increased startle reflex
    • mice exhibit an exaggerated response to stimuli (110 db) starting at 38-44 days of age   (MGI Ref ID J:179744)
  • growth/size/body phenotype
  • abnormal olfactory epithelium morphology
    • the olfactory epithelium is disorganized and shows increased expression of galectin-3, especially near the basal membrane, indicating increased inflammatory processes   (MGI Ref ID J:209834)
    • staining for a marker (olfactory marker protein) of mature olfactory cells is reduced in the olfactory epithelium   (MGI Ref ID J:209834)
    • abnormal olfactory sensory neuron morphology
      • architecture of olfactory receptor neurons is disturbed, showing enlarged gap-like spaces in the basal and middle portions of the epithelium   (MGI Ref ID J:209834)
  • decreased body weight
    • adults, but not young mice, show reduced body weight   (MGI Ref ID J:209834)
    • weight loss
      • significant weight loss observed at 6-7 weeks of age as compared to controls   (MGI Ref ID J:179744)
  • hematopoietic system phenotype
  • enlarged spleen
    • difference in weight from wild-type becomes significant at 40 days of age, but is no longer significant at 60 days probably due to wasting   (MGI Ref ID J:179744)
  • microgliosis
    • microgliosis is seen in the olfactory epithelium and olfactory bulb   (MGI Ref ID J:209834)
    • massive glia activation in the interface between axons of incoming olfactory receptor neurons and mitral cells/periglomerular cells in the olfactory bulb without neuronal loss in this area   (MGI Ref ID J:209834)
  • immune system phenotype
  • enlarged spleen
    • difference in weight from wild-type becomes significant at 40 days of age, but is no longer significant at 60 days probably due to wasting   (MGI Ref ID J:179744)
  • microgliosis
    • microgliosis is seen in the olfactory epithelium and olfactory bulb   (MGI Ref ID J:209834)
    • massive glia activation in the interface between axons of incoming olfactory receptor neurons and mitral cells/periglomerular cells in the olfactory bulb without neuronal loss in this area   (MGI Ref ID J:209834)
  • nasal inflammation
    • the olfactory epithelium and olfactory bulb show increased expression of galectin-3, indicating increased inflammatory processes   (MGI Ref ID J:209834)
    • macrophages are seen in the basal epithelial layer of the olfactory epithelium, crossing the basal membrane   (MGI Ref ID J:209834)
  • liver/biliary system phenotype
  • decreased liver cholesterol level
    • esterified cholesterol in liver tissue decreases with age   (MGI Ref ID J:179744)
  • enlarged liver   (MGI Ref ID J:179744)
  • increased liver cholesterol level
    • unesterified cholesterol in liver tissue increases with age   (MGI Ref ID J:179744)
  • mortality/aging
  • partial lethality
    • heterozygote matings produce less than the expected ratio of homozygotes (16-18% vs. 25%)   (MGI Ref ID J:179744)
  • premature death
    • average lifespan is 74 +/- 1.7 days   (MGI Ref ID J:179744)
  • vision/eye phenotype
  • abnormal cornea morphology
    • corneal basal cells do not have distinguishable borders and cytoplasm   (MGI Ref ID J:182268)
    • corneas exhibit an increase in dendritic cell number   (MGI Ref ID J:182268)
    • corneal deposits
      • corneas exhibit hyperreflective inclusions in intermediate and basal cells   (MGI Ref ID J:182268)
      • treatment with cyclodextrin/allopregnanolone results in regression of corneal inclusions   (MGI Ref ID J:182268)
  • craniofacial phenotype
  • abnormal olfactory epithelium morphology
    • the olfactory epithelium is disorganized and shows increased expression of galectin-3, especially near the basal membrane, indicating increased inflammatory processes   (MGI Ref ID J:209834)
    • staining for a marker (olfactory marker protein) of mature olfactory cells is reduced in the olfactory epithelium   (MGI Ref ID J:209834)
    • abnormal olfactory sensory neuron morphology
      • architecture of olfactory receptor neurons is disturbed, showing enlarged gap-like spaces in the basal and middle portions of the epithelium   (MGI Ref ID J:209834)
  • respiratory system phenotype
  • abnormal olfactory epithelium morphology
    • the olfactory epithelium is disorganized and shows increased expression of galectin-3, especially near the basal membrane, indicating increased inflammatory processes   (MGI Ref ID J:209834)
    • staining for a marker (olfactory marker protein) of mature olfactory cells is reduced in the olfactory epithelium   (MGI Ref ID J:209834)
    • abnormal olfactory sensory neuron morphology
      • architecture of olfactory receptor neurons is disturbed, showing enlarged gap-like spaces in the basal and middle portions of the epithelium   (MGI Ref ID J:209834)
  • nasal inflammation
    • the olfactory epithelium and olfactory bulb show increased expression of galectin-3, indicating increased inflammatory processes   (MGI Ref ID J:209834)
    • macrophages are seen in the basal epithelial layer of the olfactory epithelium, crossing the basal membrane   (MGI Ref ID J:209834)
  • taste/olfaction phenotype
  • abnormal olfactory system morphology
    • myelin-like lysosomal deposits in all types of cells of the peripheral and central olfactory system, including the supporting cells of the olfactory epithelium, the olfactory ensheathing cells of the lamina propria and central glia cells   (MGI Ref ID J:209834)
    • number of autophagosomes is high in ensheathing cells of nerve fiber layer of the olfactory bulb, in astrocytes and mitral cells and their dendrites   (MGI Ref ID J:209834)
    • abnormal olfactory epithelium morphology
      • the olfactory epithelium is disorganized and shows increased expression of galectin-3, especially near the basal membrane, indicating increased inflammatory processes   (MGI Ref ID J:209834)
      • staining for a marker (olfactory marker protein) of mature olfactory cells is reduced in the olfactory epithelium   (MGI Ref ID J:209834)
      • abnormal olfactory sensory neuron morphology
        • architecture of olfactory receptor neurons is disturbed, showing enlarged gap-like spaces in the basal and middle portions of the epithelium   (MGI Ref ID J:209834)
  • impaired olfaction
    • olfaction is impaired as shown by decreased amplitudes in electro-olfactogram recordings after exposure of olfactory epithelium to different olfactory (phenyl ethyl alcohol and hydrogen sulfide) and trigeminal stimuli (carbon dioxide)   (MGI Ref ID J:209834)

Npc1m1N/Npc1m1N

        involves: BALB/c * C57BL/6 * CBA
  • mortality/aging
  • premature death
    • animals die between 85-95 days of age   (MGI Ref ID J:144240)
  • growth/size/body phenotype
  • weight loss
    • animals start to lose weight at weeks 5 to 6   (MGI Ref ID J:144240)
  • nervous system phenotype
  • abnormal microglial cell physiology
    • cerebellar tissue samples display large accumulation of microglia with amoeboid morphology typical of activated cells whereas control tissue contains only resting microglia   (MGI Ref ID J:144240)
  • homeostasis/metabolism phenotype
  • abnormal phospholipid level
    • 80-day-old mice have increased levels of GM2 and GM3 gangliosides in the cerebral cortex compared to wild-type controls which exhibit no storage of gangliosides   (MGI Ref ID J:144240)
  • immune system phenotype
  • abnormal microglial cell physiology
    • cerebellar tissue samples display large accumulation of microglia with amoeboid morphology typical of activated cells whereas control tissue contains only resting microglia   (MGI Ref ID J:144240)
  • hematopoietic system phenotype
  • abnormal microglial cell physiology
    • cerebellar tissue samples display large accumulation of microglia with amoeboid morphology typical of activated cells whereas control tissue contains only resting microglia   (MGI Ref ID J:144240)

Npc1m1N/Npc1m1N

        B6.C-Npc1m1N
  • nervous system phenotype
  • Purkinje cell degeneration
  • astrocytosis   (MGI Ref ID J:157113)
  • microgliosis   (MGI Ref ID J:157113)
  • hematopoietic system phenotype
  • microgliosis   (MGI Ref ID J:157113)
  • homeostasis/metabolism phenotype
  • increased cholesterol level
    • mice exhibit an increase in unestrified cholesterol in the cerebellum compared with wild-type mice   (MGI Ref ID J:157113)
  • cellular phenotype
  • foam cell reticulosis
    • mice exhibit proliferation of foamy cells in the liver unlike wild-type mice   (MGI Ref ID J:157113)
  • immune system phenotype
  • microgliosis   (MGI Ref ID J:157113)

Npc1m1N/Npc1m1N

        BALB/c-Npc1m1N
  • mortality/aging
  • premature death
    • mutants start to die at 73 days of age   (MGI Ref ID J:172769)
  • growth/size/body phenotype
  • weight loss
    • mutants exhibit a progressive weight loss from 4 weeks of age   (MGI Ref ID J:172769)
  • nervous system phenotype
  • Purkinje cell degeneration
    • lower number of surviving Purkinje cells in cerebellar lobes VIII and X   (MGI Ref ID J:172769)
  • astrocytosis
    • increase in astrocytosis and microglia activation   (MGI Ref ID J:172769)
  • decreased brain size   (MGI Ref ID J:172769)
  • demyelination
    • mutants exhibit demyelination in the white matter   (MGI Ref ID J:172769)
  • increased brain cholesterol level
    • mutants exhibit vesicular accumulation of cholesterol in the cerebellum   (MGI Ref ID J:172769)
  • behavior/neurological phenotype
  • impaired coordination
    • progressive decline in motor coordination after 4 weeks of age   (MGI Ref ID J:172769)
  • homeostasis/metabolism phenotype
  • increased brain cholesterol level
    • mutants exhibit vesicular accumulation of cholesterol in the cerebellum   (MGI Ref ID J:172769)

Npc1m1N/Npc1m1N

        involves: BALB/c * C3H/HeJ * C57BL/6J
  • mortality/aging
  • premature death
    • mutants exhibit a reduced lifespan with only 30% of mice living past 90 days   (MGI Ref ID J:188345)
    • mutants treated with 2-hydroxypropyl-beta-cyclodextrin (2-HPC) at P7 to lower cholesterol accumulation live significantly longer than saline-injected mutants, with a median survival of 107 days versus 85 days   (MGI Ref ID J:188345)
  • behavior/neurological phenotype
  • abnormal object recognition memory
    • mutants exhibit deficits in object memory index at 10 weeks of age, but not at 7 weeks of age, on the object recognition memory test   (MGI Ref ID J:188345)
    • mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in cognitive performance   (MGI Ref ID J:188345)
  • hypoactivity
    • mutants exhibit reduced locomotor activity and increased periods of inactivity in open-field tests at 10 weeks of age   (MGI Ref ID J:188345)
    • mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance   (MGI Ref ID J:188345)
  • impaired coordination
    • mutants exhibit impaired rotarod performance and gait coordination at 10 weeks of age but not at 4 or 7 weeks of age   (MGI Ref ID J:188345)
    • mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance   (MGI Ref ID J:188345)
  • nervous system phenotype
  • demyelination
    • mutants exhibit demyelination in the hippocampus/cortex and cerebellum, however demyelination is less severe than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants at earlier stages   (MGI Ref ID J:188345)
  • increased brain cholesterol level
    • mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age   (MGI Ref ID J:188345)
    • however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls   (MGI Ref ID J:188345)
  • microgliosis
    • mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants   (MGI Ref ID J:188345)
    • mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants   (MGI Ref ID J:188345)
  • neurodegeneration
    • neurodgeneration in the cerebellum   (MGI Ref ID J:188345)
    • Purkinje cell degeneration
      • decrease in the number of cerebellar Purkinje cells; cell loss is less pronounced than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants   (MGI Ref ID J:188345)
      • however neuronal loss in the hippocampus is not seen   (MGI Ref ID J:188345)
      • mutants treated with 2-HPC at P7 to lower cholesterol accumulation show decreased Purkinje cell loss compared to saline-injected mutants   (MGI Ref ID J:188345)
  • hematopoietic system phenotype
  • microgliosis
    • mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants   (MGI Ref ID J:188345)
    • mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants   (MGI Ref ID J:188345)
  • homeostasis/metabolism phenotype
  • abnormal enzyme/ coenzyme level
    • cathepsin D levels and activity are higher in the hippocampus and the cerebellum than in controls, although this is lower than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants   (MGI Ref ID J:188345)
    • cytosolic cathepsin D, cytochrome c and Bcl-2-associated X protein levels are increased in the cerebellum although to a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants   (MGI Ref ID J:188345)
  • increased brain cholesterol level
    • mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age   (MGI Ref ID J:188345)
    • however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls   (MGI Ref ID J:188345)
  • immune system phenotype
  • microgliosis
    • mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants   (MGI Ref ID J:188345)
    • mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants   (MGI Ref ID J:188345)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Internal/Organ Research
Liver Defects
Spleen Defects

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
Metabolic Defects
Myelination Defects
Neurodegeneration
Tremor Defects

Npc1m1N related

Internal/Organ Research
Liver Defects
Spleen Defects

Metabolism Research

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
Metabolic Defects
Myelination Defects
Neurodegeneration
Neuromuscular Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Npc1m1N
Allele Name Niemann Pick type C1 NIH
Allele Type Spontaneous
Common Name(s) -npc; CSD; NPC; NPC1; NPC1-; Npc-; Npc1N; lcsd; lysosomal cholesterol storage disease; nctr; npc1NIH; npcnih;
Strain of OriginBALB/c
Gene Symbol and Name Npc1, Niemann-Pick type C1
Chromosome 18
Gene Common Name(s) A430089E03Rik; C85354; Cdig2; D18Ertd139e; D18Ertd723e; DNA segment, Chr 18, ERATO Doi 139, expressed; DNA segment, Chr 18, ERATO Doi 723, expressed; NPC; RIKEN cDNA A430089E03 gene; expressed sequence C85354; lcsd; lysosomal cholesterol storage disease; neuroscience mutagenesis facility, 164; nmf164; sphingomyelinosis; spm;
Molecular Note 824 bp of MaLR retroposon-like DNA replaced 703 bp of wild-type genomic sequence spanning 44 bp of an exon and 659 bp of the downstream intron. The insertion results in premature truncation of the protein deleting 11 out of 13 transmembrane domains. Northern blot analysis revealed marked decrease in gene expression in liver and brain from homozygous mutant animals. [MGI Ref ID J:41469]

Genotyping

Genotyping Information

Genotyping Protocols

Npc1, Melt Curve Analysis
Tg(tetO-Npc1/YFP)1Mps alternate1,

MELT


Npc1m1N, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lopez ME; Klein AD; Dimbil UJ; Scott MP. 2011. Anatomically defined neuron-based rescue of neurodegenerative niemann-pick type C disorder. J Neurosci 31(12):4367-78. [PubMed: 21430138]  [MGI Ref ID J:170312]

Additional References

Npc1m1N related

Abi-Mosleh L; Infante RE; Radhakrishnan A; Goldstein JL; Brown MS. 2009. Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells. Proc Natl Acad Sci U S A 106(46):19316-21. [PubMed: 19884502]  [MGI Ref ID J:154766]

Alam MS; Getz M; Safeukui I; Yi S; Tamez P; Shin J; Velazquez P; Haldar K. 2012. Genomic expression analyses reveal lysosomal, innate immunity proteins, as disease correlates in murine models of a lysosomal storage disorder. PLoS One 7(10):e48273. [PubMed: 23094108]  [MGI Ref ID J:192177]

Alam MS; Getz M; Yi S; Kurkewich J; Safeukui I; Haldar K. 2014. Plasma signature of neurological disease in the monogenetic disorder Niemann-Pick Type C. J Biol Chem 289(12):8051-66. [PubMed: 24488491]  [MGI Ref ID J:211208]

Alvarez AR; Klein A; Castro J; Cancino GI; Amigo J; Mosqueira M; Vargas LM; Yevenes LF; Bronfman FC; Zanlungo S. 2008. Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease. FASEB J 22(10):3617-27. [PubMed: 18591368]  [MGI Ref ID J:140248]

Amigo L; Mendoza H; Castro J; Quinones V; Miquel JF; Zanlungo S. 2002. Relevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice. Hepatology 36(4 Pt 1):819-28. [PubMed: 12297829]  [MGI Ref ID J:106027]

Amritraj A; Peake K; Kodam A; Salio C; Merighi A; Vance JE; Kar S. 2009. Increased activity and altered subcellular distribution of lysosomal enzymes determine neuronal vulnerability in Niemann-Pick type C1-deficient mice. Am J Pathol 175(6):2540-56. [PubMed: 19893049]  [MGI Ref ID J:155318]

Aqul A; Liu B; Ramirez CM; Pieper AA; Estill SJ; Burns DK; Liu B; Repa JJ; Turley SD; Dietschy JM. 2011. Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment. J Neurosci 31(25):9404-13. [PubMed: 21697390]  [MGI Ref ID J:173597]

Avchalumov Y; Kirschstein T; Lukas J; Luo J; Wree A; Rolfs A; Kohling R. 2012. Increased excitability and compromised long-term potentiation in the neocortex of NPC1(-/-) mice. Brain Res 1444:20-6. [PubMed: 22325094]  [MGI Ref ID J:181851]

Baudry M; Yao Y; Simmons D; Liu J; Bi X. 2003. Postnatal development of inflammation in a murine model of Niemann-Pick type C disease: immunohistochemical observations of microglia and astroglia. Exp Neurol 184(2):887-903. [PubMed: 14769381]  [MGI Ref ID J:87264]

Beltroy EP; Liu B; Dietschy JM; Turley SD. 2007. Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease. J Lipid Res 48(4):869-81. [PubMed: 17220530]  [MGI Ref ID J:121676]

Bhuvaneswaran C; Morris MD; Shio H; Fowler S. 1982. Lysosome lipid storage disorder in NCTR-BALB/c mice. III. Isolation and analysis of storage inclusions from liver. Am J Pathol 108(2):160-70. [PubMed: 6101077]  [MGI Ref ID J:10214]

Bi X; Liu J; Yao Y; Baudry M; Lynch G. 2005. Deregulation of the phosphatidylinositol-3 kinase signaling cascade is associated with neurodegeneration in Npc1-/- mouse brain. Am J Pathol 167(4):1081-92. [PubMed: 16192643]  [MGI Ref ID J:101694]

Boland B; Smith DA; Mooney D; Jung SS; Walsh DM; Platt FM. 2010. Macroautophagy is not directly involved in the metabolism of amyloid precursor protein. J Biol Chem 285(48):37415-26. [PubMed: 20864542]  [MGI Ref ID J:167334]

Boothe AD; Bhuvaneswaran C; Morris MD; Barry JE. 1977. Tissue cholesterol storage disorder in BALB/c mice: histologic findings Fed Proc 36:1158 (Abstr.).  [MGI Ref ID J:83825]

Bosch B; Berger AC; Khandelwal S; Heipertz EL; Scharf B; Santambrogio L; Roche PA. 2013. Disruption of multivesicular body vesicles does not affect major histocompatibility complex (MHC) class II-peptide complex formation and antigen presentation by dendritic cells. J Biol Chem 288(34):24286-92. [PubMed: 23846690]  [MGI Ref ID J:203447]

Bu B; Li J; Davies P; Vincent I. 2002. Deregulation of cdk5, hyperphosphorylation, and cytoskeletal pathology in the Niemann-Pick type C murine model. J Neurosci 22(15):6515-25. [PubMed: 12151531]  [MGI Ref ID J:78091]

Burns M; Gaynor K; Olm V; Mercken M; LaFrancois J; Wang L; Mathews PM; Noble W; Matsuoka Y; Duff K. 2003. Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo. J Neurosci 23(13):5645-9. [PubMed: 12843267]  [MGI Ref ID J:84370]

Carette JE; Raaben M; Wong AC; Herbert AS; Obernosterer G; Mulherkar N; Kuehne AI; Kranzusch PJ; Griffin AM; Ruthel G; Dal Cin P; Dye JM; Whelan SP; Chandran K; Brummelkamp TR. 2011. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477(7364):340-3. [PubMed: 21866103]  [MGI Ref ID J:176235]

Chen G; Li HM; Chen YR; Gu XS; Duan S. 2007. Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C. Glia 55(15):1509-18. [PubMed: 17705200]  [MGI Ref ID J:156298]

Claudepierre T; Paques M; Simonutti M; Buard I; Sahel J; Maue RA; Picaud S; Pfrieger FW. 2010. Lack of Niemann-Pick type C1 induces age-related degeneration in the mouse retina. Mol Cell Neurosci 43(1):164-76. [PubMed: 19883762]  [MGI Ref ID J:158305]

D'Arcangelo G; Grossi D; De Chiara G; de Stefano MC; Cortese G; Citro G; Rufini S; Tancredi V; Merlo D; Frank C. 2011. Glutamatergic neurotransmission in a mouse model of Niemann-Pick Type C Disease. Brain Res 1396:11-9. [PubMed: 21575932]  [MGI Ref ID J:172649]

Deisz RA; Meske V; Treiber-Held S; Albert F; Ohm TG. 2005. Pathological cholesterol metabolism fails to modify electrophysiological properties of afflicted neurones in Niemann-Pick disease type C. Neuroscience 130(4):867-73. [PubMed: 15652985]  [MGI Ref ID J:105214]

Dixit SS; Jadot M; Sohar I; Sleat DE; Stock AM; Lobel P. 2011. Loss of niemann-pick c1 or c2 protein results in similar biochemical changes suggesting that these proteins function in a common lysosomal pathway. PLoS One 6(8):e23677. [PubMed: 21887293]  [MGI Ref ID J:176152]

Dixit SS; Sleat DE; Stock AM; Lobel P. 2007. Do mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption? Biochem J 408(1):1-5. [PubMed: 17880278]  [MGI Ref ID J:126287]

Elrick MJ; Pacheco CD; Yu T; Dadgar N; Shakkottai VG; Ware C; Paulson HL; Lieberman AP. 2010. Conditional Niemann-Pick C mice demonstrate cell autonomous Purkinje cell neurodegeneration. Hum Mol Genet 19(5):837-47. [PubMed: 20007718]  [MGI Ref ID J:157113]

Elrick MJ; Yu T; Chung C; Lieberman AP. 2012. Impaired proteolysis underlies autophagic dysfunction in Niemann-Pick type C disease. Hum Mol Genet 21(22):4876-87. [PubMed: 22872701]  [MGI Ref ID J:188344]

Erickson RP; Bhattacharyya A; Hunter RJ; Heidenreich RA; Cherrington NJ. 2005. Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet. Am J Physiol Gastrointest Liver Physiol 289(2):G300-7. [PubMed: 15790756]  [MGI Ref ID J:100351]

Erickson RP; Garver WS; Camargo F; Hossain GS; Heidenreich RA. 2000. Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann-Pick C mice J Inherit Metab Dis 23(1):54-62. [PubMed: 10682308]  [MGI Ref ID J:60459]

Erickson RP; Kiela M; Devine PJ; Hoyer PB; Heidenreich RA. 2002. mdr1a deficiency corrects sterility in Niemann-Pick C1 protein deficient female mice. Mol Reprod Dev 62(2):167-73. [PubMed: 11984826]  [MGI Ref ID J:76395]

Erickson RP; Kiela M; Garver WS; Krishnan K; Heidenreich RA. 2001. Cholesterol signaling at the endoplasmic reticulum occurs in npc1(-/-) but not in npc1(-/-), LDLR(-/-) mice. Biochem Biophys Res Commun 284(2):326-30. [PubMed: 11394880]  [MGI Ref ID J:69915]

Fan J; Akabane H; Graham SN; Richardson LL; Zhu GZ. 2006. Sperm defects in mice lacking a functional Niemann-Pick C1 protein. Mol Reprod Dev 73(10):1284-91. [PubMed: 16850391]  [MGI Ref ID J:119302]

Fan M; Sidhu R; Fujiwara H; Tortelli B; Zhang J; Davidson C; Walkley SU; Bagel JH; Vite C; Yanjanin NM; Porter FD; Schaffer JE; Ory DS. 2013. Identification of Niemann-Pick C1 disease biomarkers through sphingolipid profiling. J Lipid Res 54(10):2800-14. [PubMed: 23881911]  [MGI Ref ID J:202626]

Fu R; Wassif CA; Yanjanin NM; Watkins-Chow DE; Baxter LL; Incao A; Liscum L; Sidhu R; Firnkes S; Graham M; Ory DS; Porter FD; Pavan WJ. 2013. Efficacy of N-acetylcysteine in phenotypic suppression of mouse models of Niemann-Pick disease, type C1. Hum Mol Genet 22(17):3508-23. [PubMed: 23666527]  [MGI Ref ID J:199190]

Gadola SD; Silk JD; Jeans A; Illarionov PA; Salio M; Besra GS; Dwek R; Butters TD; Platt FM; Cerundolo V. 2006. Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J Exp Med 203(10):2293-303. [PubMed: 16982810]  [MGI Ref ID J:124639]

German DC; Liang CL; Song T; Yazdani U; Xie C; Dietschy JM. 2002. Neurodegeneration in the Niemann-Pick C mouse: glial involvement. Neuroscience 109(3):437-50. [PubMed: 11823057]  [MGI Ref ID J:126856]

German DC; Quintero EM; Liang C; Xie C; Dietschy JM. 2001. Degeneration of neurons and glia in the Niemann-Pick C mouse is unrelated to the low-density lipoprotein receptor. Neuroscience 105(4):999-1005. [PubMed: 11530237]  [MGI Ref ID J:126474]

Gevry NY; Lopes FL; Ledoux S; Murphy BD. 2004. Aberrant intracellular cholesterol transport disrupts pituitary and ovarian function. Mol Endocrinol 18(7):1778-86. [PubMed: 15105438]  [MGI Ref ID J:91430]

Gevry NY; Murphy BD. 2002. The role and regulation of the Niemann-Pick C1 gene in adrenal steroidogenesis. Endocr Res 28(4):403-12. [PubMed: 12530642]  [MGI Ref ID J:91497]

Gondre-Lewis MC; McGlynn R; Walkley SU. 2003. Cholesterol accumulation in NPC1-deficient neurons is ganglioside dependent. Curr Biol 13(15):1324-9. [PubMed: 12906793]  [MGI Ref ID J:95799]

Goodrum JF; Pentchev PG. 1997. Cholesterol reutilization during myelination of regenerating PNS axons is impaired in Niemann-Pick disease type C mice. J Neurosci Res 49(3):389-92. [PubMed: 9260750]  [MGI Ref ID J:42120]

Griffin LD; Gong W; Verot L; Mellon SH. 2004. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat Med 10(7):704-11. [PubMed: 15208706]  [MGI Ref ID J:91682]

Hallows JL; Iosif RE; Biasell RD; Vincent I. 2006. p35/p25 is not essential for tau and cytoskeletal pathology or neuronal loss in Niemann-Pick type C disease. J Neurosci 26(10):2738-44. [PubMed: 16525053]  [MGI Ref ID J:106228]

Hawes CM; Wiemer H; Krueger SR; Karten B. 2010. Pre-synaptic defects of NPC1-deficient hippocampal neurons are not directly related to plasma membrane cholesterol. J Neurochem 114(1):311-22. [PubMed: 20456004]  [MGI Ref ID J:161819]

Henderson LP; Lin L; Prasad A; Paul CA; Chang TY; Maue RA. 2000. Embryonic striatal neurons from niemann-pick type C mice exhibit defects in cholesterol metabolism and neurotrophin responsiveness. J Biol Chem 275(26):20179-87. [PubMed: 10770933]  [MGI Ref ID J:110802]

Higashi Y; Murayama S; Pentchev PG; Suzuki K. 1993. Cerebellar degeneration in the Niemann-Pick type C mouse. Acta Neuropathol (Berl) 85(2):175-84. [PubMed: 8382896]  [MGI Ref ID J:4992]

Higashi Y; Murayama S; Pentchev PG; Suzuki K. 1995. Peripheral nerve pathology in Niemann-Pick type C mouse. Acta Neuropathol (Berl) 90(2):158-63. [PubMed: 7484091]  [MGI Ref ID J:28629]

Holtta-Vuori M; Vainio S; Kauppi M; Van Eck M; Jokitalo E; Ikonen E. 2012. Endosomal actin remodeling by coronin-1A controls lipoprotein uptake and degradation in macrophages. Circ Res 110(3):450-5. [PubMed: 22223354]  [MGI Ref ID J:192698]

Hovakimyan M; Maass F; Petersen J; Holzmann C; Witt M; Lukas J; Frech MJ; Hubner R; Rolfs A; Wree A. 2013. Combined therapy with cyclodextrin/allopregnanolone and miglustat improves motor but not cognitive functions in Niemann-Pick Type C1 mice. Neuroscience 252:201-11. [PubMed: 23948640]  [MGI Ref ID J:207440]

Hovakimyan M; Meyer A; Lukas J; Luo J; Gudziol V; Hummel T; Rolfs A; Wree A; Witt M. 2013. Olfactory deficits in Niemann-Pick type C1 (NPC1) disease. PLoS One 8(12):e82216. [PubMed: 24391715]  [MGI Ref ID J:209834]

Hovakimyan M; Petersen J; Maass F; Reichard M; Witt M; Lukas J; Stachs O; Guthoff R; Rolfs A; Wree A. 2011. Corneal alterations during combined therapy with cyclodextrin/allopregnanolone and miglustat in a knock-out mouse model of NPC1 disease. PLoS One 6(12):e28418. [PubMed: 22163015]  [MGI Ref ID J:182268]

Ishibashi M; Masson D; Westerterp M; Wang N; Sayers S; Li R; Welch CL; Tall AR. 2010. Reduced VLDL clearance in Apoe(-/-)Npc1(-/-) mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels. J Lipid Res 51(9):2655-63. [PubMed: 20562239]  [MGI Ref ID J:164461]

Jelinek D; Castillo JJ; Garver WS. 2013. The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage has impaired glucose tolerance independent of body weight. Gene 527(1):65-70. [PubMed: 23769925]  [MGI Ref ID J:200780]

Jelinek D; Millward V; Birdi A; Trouard TP; Heidenreich RA; Garver WS. 2011. Npc1 haploinsufficiency promotes weight gain and metabolic features associated with insulin resistance. Hum Mol Genet 20(2):312-21. [PubMed: 21036943]  [MGI Ref ID J:166906]

Jelinek DA; Maghsoodi B; Borbon IA; Hardwick RN; Cherrington NJ; Erickson RP. 2012. Genetic variation in the mouse model of Niemann Pick C1 affects female, as well as male, adiposity, and hepatic bile transporters but has indeterminate effects on caveolae. Gene 491(2):128-34. [PubMed: 22020183]  [MGI Ref ID J:179071]

Kaptzan T; West SA; Holicky EL; Wheatley CL; Marks DL; Wang T; Peake KB; Vance J; Walkley SU; Pagano RE. 2009. Development of a Rab9 transgenic mouse and its ability to increase the lifespan of a murine model of Niemann-Pick type C disease. Am J Pathol 174(1):14-20. [PubMed: 19056848]  [MGI Ref ID J:144240]

Karten B; Campenot RB; Vance DE; Vance JE. 2006. The Niemann-Pick C1 protein in recycling endosomes of presynaptic nerve terminals. J Lipid Res 47(3):504-14. [PubMed: 16340014]  [MGI Ref ID J:107557]

Karten B; Hayashi H; Francis GA; Campenot RB; Vance DE; Vance JE. 2005. Generation and function of astroglial lipoproteins from Niemann-Pick type C1-deficient mice. Biochem J 387(Pt 3):779-88. [PubMed: 15544574]  [MGI Ref ID J:117523]

Karten B; Vance DE; Campenot RB; Vance JE. 2002. Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons. J Neurochem 83(5):1154-63. [PubMed: 12437586]  [MGI Ref ID J:80447]

Karten B; Vance DE; Campenot RB; Vance JE. 2003. Trafficking of Cholesterol from Cell Bodies to Distal Axons in Niemann Pick C1-deficient Neurons. J Biol Chem 278(6):4168-75. [PubMed: 12458210]  [MGI Ref ID J:81676]

Kennedy BE; LeBlanc VG; Mailman TM; Fice D; Burton I; Karakach TK; Karten B. 2013. Pre-symptomatic activation of antioxidant responses and alterations in glucose and pyruvate metabolism in Niemann-Pick Type C1-deficient murine brain. PLoS One 8(12):e82685. [PubMed: 24367541]  [MGI Ref ID J:211133]

Kim MJ; Kim J; Hutchinson B; Michikawa M; Cha CI; Lee B. 2005. Substance P immunoreactive cell reductions in cerebral cortex of Niemann-Pick disease type C mouse. Brain Res 1043(1-2):218-24. [PubMed: 15862536]  [MGI Ref ID J:98024]

Kim SJ; Lee BH; Lee YS; Kang KS. 2007. Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-Pick type C disease improved by valproic acid, a histone deacetylase inhibitor. Biochem Biophys Res Commun 360(3):593-599. [PubMed: 17624314]  [MGI Ref ID J:123024]

Klein A; Amigo L; Retamal MJ; Morales MG; Miquel JF; Rigotti A; Zanlungo S. 2006. NPC2 is expressed in human and murine liver and secreted into bile: potential implications for body cholesterol homeostasis. Hepatology 43(1):126-33. [PubMed: 16374838]  [MGI Ref ID J:115647]

Klein A; Maldonado C; Vargas LM; Gonzalez M; Robledo F; Perez de Arce K; Munoz FJ; Hetz C; Alvarez AR; Zanlungo S. 2011. Oxidative stress activates the c-Abl/p73 proapoptotic pathway in Niemann-Pick type C neurons. Neurobiol Dis 41(1):209-18. [PubMed: 20883783]  [MGI Ref ID J:167246]

Ko DC; Milenkovic L; Beier SM; Manuel H; Buchanan J; Scott MP. 2005. Cell-autonomous death of cerebellar purkinje neurons with autophagy in niemann-pick type C disease. PLoS Genet 1(1):e7. [PubMed: 16103921]  [MGI Ref ID J:100117]

Kodam A; Maulik M; Peake K; Amritraj A; Vetrivel KS; Thinakaran G; Vance JE; Kar S. 2010. Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann-Pick type C1-deficient mouse brains. Glia 58(11):1267-81. [PubMed: 20607864]  [MGI Ref ID J:168042]

Kulinski A; Vance JE. 2007. Lipid homeostasis and lipoprotein secretion in Niemann-Pick C1-deficient hepatocytes. J Biol Chem 282(3):1627-37. [PubMed: 17107950]  [MGI Ref ID J:118542]

Langmade SJ; Gale SE; Frolov A; Mohri I; Suzuki K; Mellon SH; Walkley SU; Covey DF; Schaffer JE; Ory DS. 2006. Pregnane X receptor (PXR) activation: a mechanism for neuroprotection in a mouse model of Niemann-Pick C disease. Proc Natl Acad Sci U S A 103(37):13807-12. [PubMed: 16940355]  [MGI Ref ID J:113746]

Li H; Repa JJ; Valasek MA; Beltroy EP; Turley SD; German DC; Dietschy JM. 2005. Molecular, anatomical, and biochemical events associated with neurodegeneration in mice with Niemann-Pick type C disease. J Neuropathol Exp Neurol 64(4):323-33. [PubMed: 15835268]  [MGI Ref ID J:104844]

Li H; Turley SD; Liu B; Repa JJ; Dietschy JM. 2008. GM2/GD2 and GM3 gangliosides have no effect on cellular cholesterol pools or turnover in normal or NPC1 mice. J Lipid Res 49(8):1816-28. [PubMed: 18450647]  [MGI Ref ID J:138451]

Liao G; Cheung S; Galeano J; Ji AX; Qin Q; Bi X. 2009. Allopregnanolone treatment delays cholesterol accumulation and reduces autophagic/lysosomal dysfunction and inflammation in Npc1-/- mouse brain. Brain Res 1270:140-51. [PubMed: 19328188]  [MGI Ref ID J:156575]

Liao G; Yao Y; Liu J; Yu Z; Cheung S; Xie A; Liang X; Bi X. 2007. Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in npc1 / mouse brain. Am J Pathol 171(3):962-75. [PubMed: 17631520]  [MGI Ref ID J:124305]

Liu B; Li H; Repa JJ; Turley SD; Dietschy JM. 2008. Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J Lipid Res 49(3):663-9. [PubMed: 18077828]  [MGI Ref ID J:133425]

Liu B; Ramirez CM; Miller AM; Repa JJ; Turley SD; Dietschy JM. 2010. Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid. J Lipid Res 51(5):933-44. [PubMed: 19965601]  [MGI Ref ID J:160197]

Liu B; Turley SD; Burns DK; Miller AM; Repa JJ; Dietschy JM. 2009. Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse. Proc Natl Acad Sci U S A 106(7):2377-82. [PubMed: 19171898]  [MGI Ref ID J:146298]

Liu B; Xie C; Richardson JA; Turley SD; Dietschy JM. 2007. Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease. J Lipid Res 48(8):1710-23. [PubMed: 17476031]  [MGI Ref ID J:123778]

Liu Y; Wu YP; Wada R; Neufeld EB; Mullin KA; Howard AC; Pentchev PG; Vanier MT; Suzuki K; Proia RL. 2000. Alleviation of neuronal ganglioside storage does not improve the clinical course of the Niemann-Pick C disease mouse. Hum Mol Genet 9(7):1087-92. [PubMed: 10767333]  [MGI Ref ID J:61777]

Lloyd-Evans E; Morgan AJ; He X; Smith DA; Elliot-Smith E; Sillence DJ; Churchill GC; Schuchman EH; Galione A; Platt FM. 2008. Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14(11):1247-55. [PubMed: 18953351]  [MGI Ref ID J:144082]

Loftus SK; Erickson RP; Walkley SU; Bryant MA; Incao A; Heidenreich RA; Pavan WJ. 2002. Rescue of neurodegeneration in Niemann-Pick C mice by a prion-promoter-driven Npc1 cDNA transgene. Hum Mol Genet 11(24):3107-14. [PubMed: 12417532]  [MGI Ref ID J:80487]

Loftus SK; Morris JA; Carstea ED; Gu JZ; Cummings C; Brown A ; Ellison J ; Ohno K ; Rosenfeld MA ; Tagle DA ; Pentchev PG ; Pavan WJ. 1997. Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene [see comments] Science 277(5323):232-5. [PubMed: 9211850]  [MGI Ref ID J:41469]

Lopez ME; Klein AD; Hong J; Dimbil UJ; Scott MP. 2012. Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C. Hum Mol Genet 21(13):2946-60. [PubMed: 22493001]  [MGI Ref ID J:184610]

Luan Z; Saito Y; Miyata H; Ohama E; Ninomiya H; Ohno K. 2008. Brainstem neuropathology in a mouse model of Niemann-Pick disease type C. J Neurol Sci 268(1-2):108-16. [PubMed: 18190929]  [MGI Ref ID J:139928]

Mari M; Caballero F; Colell A; Morales A; Caballeria J; Fernandez A; Enrich C; Fernandez-Checa JC; Garcia-Ruiz C. 2006. Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab 4(3):185-98. [PubMed: 16950136]  [MGI Ref ID J:129725]

Maue RA; Burgess RW; Wang B; Wooley CM; Seburn KL; Vanier MT; Rogers MA; Chang CC; Chang TY; Harris BT; Graber DJ; Penatti CA; Porter DM; Szwergold BS; Henderson LP; Totenhagen JW; Trouard TP; Borbon IA; Erickson RP. 2012. A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations. Hum Mol Genet 21(4):730-50. [PubMed: 22048958]  [MGI Ref ID J:179744]

Maulik M; Ghoshal B; Kim J; Wang Y; Yang J; Westaway D; Kar S. 2012. Mutant human APP exacerbates pathology in a mouse model of NPC and its reversal by a beta-cyclodextrin. Hum Mol Genet 21(22):4857-75. [PubMed: 22869680]  [MGI Ref ID J:188345]

Maulik M; Thinakaran G; Kar S. 2013. Alterations in gene expression in mutant amyloid precursor protein transgenic mice lacking Niemann-Pick type C1 protein. PLoS One 8(1):e54605. [PubMed: 23382922]  [MGI Ref ID J:195915]

Morris MD; Bhuvaneswaran C; Boothe AD. 1977. Tissue cholesterol storage disorder in BALB/c mice Fed Proc 36:1158 (Abstr.).  [MGI Ref ID J:83826]

Morris MD; Bhuvaneswaran C; Shio H; Fowler S. 1982. Lysosome lipid storage disorder in NCTR-BALB/c mice. I. Description of the disease and genetics. Am J Pathol 108(2):140-9. [PubMed: 6765731]  [MGI Ref ID J:10212]

Muralidhar A; Borbon IA; Esharif DM; Ke W; Manacheril R; Daines M; Erickson RP. 2011. Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1(-/-) mice. Mol Genet Metab 103(2):142-7. [PubMed: 21459030]  [MGI Ref ID J:172067]

Nunes A; Pressey SN; Cooper JD; Soriano S. 2011. Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis 42(3):349-59. [PubMed: 21303697]  [MGI Ref ID J:172769]

Ohara S; Ukita Y; Ninomiya H; Ohno K. 2004. Axonal dystrophy of dorsal root ganglion sensory neurons in a mouse model of Niemann-Pick disease type C. Exp Neurol 187(2):289-98. [PubMed: 15144855]  [MGI Ref ID J:94570]

Ohara S; Ukita Y; Ninomiya H; Ohno K. 2004. Degeneration of cholecystokinin-immunoreactive afferents to the VPL thalamus in a mouse model of Niemann-Pick disease type C. Brain Res 1022(1-2):244-6. [PubMed: 15353235]  [MGI Ref ID J:92532]

Ong QR; Lim ML; Chua CC; Cheung NS; Wong BS. 2012. Impaired insulin signaling in an animal model of Niemann-Pick Type C disease. Biochem Biophys Res Commun 424(3):482-7. [PubMed: 22776200]  [MGI Ref ID J:186234]

Pacheco CD; Elrick MJ; Lieberman AP. 2009. Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis. Hum Mol Genet 18(5):956-65. [PubMed: 19074461]  [MGI Ref ID J:145003]

Pacheco CD; Kunkel R; Lieberman AP. 2007. Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects. Hum Mol Genet 16(12):1495-503. [PubMed: 17468177]  [MGI Ref ID J:125097]

Parra J; Klein AD; Castro J; Morales MG; Mosqueira M; Valencia I; Cortes V; Rigotti A; Zanlungo S. 2011. Npc1 deficiency in the C57BL/6J genetic background enhances Niemann-Pick disease type C spleen pathology. Biochem Biophys Res Commun 413(3):400-6. [PubMed: 21910975]  [MGI Ref ID J:177519]

Patel SC; Suresh S; Weintroub H; Brady RO; Pentchev PG. 1987. Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant. Biochem Biophys Res Commun 143(1):233-40. [PubMed: 3827919]  [MGI Ref ID J:8620]

Peake KB; Campenot RB; Vance DE; Vance JE. 2011. Niemann-Pick Type C1 deficiency in microglia does not cause neuron death in vitro. Biochim Biophys Acta 1812(9):1121-9. [PubMed: 21704157]  [MGI Ref ID J:177615]

Pentchev PG; Boothe AD; Kruth HS; Weintroub H; Stivers J; Brady RO. 1984. A genetic storage disorder in BALB/C mice with a metabolic block in esterification of exogenous cholesterol. J Biol Chem 259(9):5784-91. [PubMed: 6325448]  [MGI Ref ID J:76734]

Pentchev PG; Brady RO; Blanchette-Mackie EJ; Vanier MT; Carstea ED; Parker CC; Goldin E; Roff CF. 1994. The Niemann-Pick C lesion and its relationship to the intracellular distribution and utilization of LDL cholesterol. Biochim Biophys Acta 1225(3):235-43. [PubMed: 8312368]  [MGI Ref ID J:83835]

Pentchev PG; Comly ME; Kruth HS; Patel S; Proestel M; Weintroub H. 1986. The cholesterol storage disorder of the mutant BALB/c mouse. A primary genetic lesion closely linked to defective esterification of exogenously derived cholesterol and its relationship to human type C Niemann-Pick disease. J Biol Chem 261(6):2772-7. [PubMed: 3949747]  [MGI Ref ID J:8198]

Pentchev PG; Gal AE; Booth AD; Omodeo-Sale F; Fouks J; Neumeyer BA; Quirk JM; Dawson G; Brady RO. 1980. A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase. Biochim Biophys Acta 619(3):669-79. [PubMed: 6257302]  [MGI Ref ID J:18511]

Porter FD; Scherrer DE; Lanier MH; Langmade SJ; Molugu V; Gale SE; Olzeski D; Sidhu R; Dietzen DJ; Fu R; Wassif CA; Yanjanin NM; Marso SP; House J; Vite C; Schaffer JE; Ory DS. 2010. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med 2(56):56ra81. [PubMed: 21048217]  [MGI Ref ID J:168029]

Pressey SN; Smith DA; Wong AM; Platt FM; Cooper JD. 2012. Early glial activation, synaptic changes and axonal pathology in the thalamocortical system of Niemann-Pick type C1 mice. Neurobiol Dis 45(3):1086-100. [PubMed: 22198570]  [MGI Ref ID J:182040]

Qin Q; Liao G; Baudry M; Bi X. 2010. Cholesterol Perturbation in Mice Results in p53 Degradation and Axonal Pathology through p38 MAPK and Mdm2 Activation. PLoS One 5(4):e9999. [PubMed: 20386595]  [MGI Ref ID J:160166]

Quan G; Xie C; Dietschy JM; Turley SD. 2003. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Brain Res Dev Brain Res 146(1-2):87-98. [PubMed: 14643015]  [MGI Ref ID J:86935]

Ramirez CM; Liu B; Aqul A; Taylor AM; Repa JJ; Turley SD; Dietschy JM. 2011. Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations. J Lipid Res 52(4):688-98. [PubMed: 21289032]  [MGI Ref ID J:170933]

Ramirez CM; Lopez AM; Le LQ; Posey KS; Weinberg AG; Turley SD. 2014. Ontogenic changes in lung cholesterol metabolism, lipid content, and histology in mice with Niemann-Pick type C disease. Biochim Biophys Acta 1841(1):54-61. [PubMed: 24076310]  [MGI Ref ID J:210049]

Reid PC; Sakashita N; Sugii S; Ohno-Iwashita Y; Shimada Y; Hickey WF; Chang TY. 2004. A novel cholesterol stain reveals early neuronal cholesterol accumulation in the Niemann-Pick type C1 mouse brain. J Lipid Res 45(3):582-91. [PubMed: 14703504]  [MGI Ref ID J:88630]

Reid PC; Sugii S; Chang TY. 2003. Trafficking defects in endogenously synthesized cholesterol in fibroblasts, macrophages, hepatocytes, and glial cells from Niemann-Pick type C1 mice. J Lipid Res 44(5):1010-9. [PubMed: 12611909]  [MGI Ref ID J:83463]

Repa JJ; Li H; Frank-Cannon TC; Valasek MA; Turley SD; Tansey MG; Dietschy JM. 2007. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J Neurosci 27(52):14470-80. [PubMed: 18160655]  [MGI Ref ID J:130969]

Roszell BR; Tao JQ; Yu KJ; Gao L; Huang S; Ning Y; Feinstein SI; Vite CH; Bates SR. 2013. Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease. PLoS One 8(7):e67084. [PubMed: 23843985]  [MGI Ref ID J:204311]

Saez PJ; Orellana JA; Vega-Riveros N; Figueroa VA; Hernandez DE; Castro JF; Klein AD; Jiang JX; Zanlungo S; Saez JC. 2013. Disruption in connexin-based communication is associated with intracellular Ca(2)(+) signal alterations in astrocytes from Niemann-Pick type C mice. PLoS One 8(8):e71361. [PubMed: 23977027]  [MGI Ref ID J:206348]

Sagiv Y; Hudspeth K; Mattner J; Schrantz N; Stern RK; Zhou D; Savage PB; Teyton L; Bendelac A. 2006. Cutting edge: impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein. J Immunol 177(1):26-30. [PubMed: 16785493]  [MGI Ref ID J:134414]

Sarkar S; Carroll B; Buganim Y; Maetzel D; Ng AH; Cassady JP; Cohen MA; Chakraborty S; Wang H; Spooner E; Ploegh H; Gsponer J; Korolchuk VI; Jaenisch R. 2013. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease. Cell Rep 5(5):1302-15. [PubMed: 24290752]  [MGI Ref ID J:206841]

Sarna JR; Larouche M; Marzban H; Sillitoe RV; Rancourt DE; Hawkes R. 2003. Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease. J Comp Neurol 456(3):279-91. [PubMed: 12528192]  [MGI Ref ID J:81305]

Sawamura N; Gong JS; Garver WS; Heidenreich RA; Ninomiya H; Ohno K; Yanagisawa K; Michikawa M. 2001. Site-specific phosphorylation of tau accompanied by activation of mitogen-activated protein kinase (MAPK) in brains of Niemann-Pick type C mice. J Biol Chem 276(13):10314-9. [PubMed: 11152466]  [MGI Ref ID J:69686]

Shio H; Fowler S; Bhuvaneswaran C; Morris MD. 1982. Lysosome lipid storage disorder in NCTR-BALB/c mice. II. Morphologic and cytochemical studies. Am J Pathol 108(2):150-9. [PubMed: 6765732]  [MGI Ref ID J:10213]

Sleat DE; Wiseman JA; El-Banna M; Price SM; Verot L; Shen MM; Tint GS; Vanier MT; Walkley SU; Lobel P. 2004. Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci U S A 101(16):5886-91. [PubMed: 15071184]  [MGI Ref ID J:89617]

Speak AO; Te Vruchte D; Davis LC; Morgan AJ; Smith DA; Yanjanin NM; Simmons L; Hartung R; Runz H; Mengel E; Beck M; Imrie J; Jacklin E; Wraith JE; Hendriksz C; Lachmann R; Cognet C; Sidhu R; Fujiwara H; Ory DS; Galione A; Porter FD; Vivier E; Platt FM. 2014. Altered distribution and function of natural killer cells in murine and human Niemann-Pick disease type C1. Blood 123(1):51-60. [PubMed: 24235134]  [MGI Ref ID J:208090]

Suresh S; Yan Z; Patel RC; Patel YC; Patel SC. 1998. Cellular cholesterol storage in the Niemann-Pick disease type C mouse is associated with increased expression and defective processing of apolipoprotein D. J Neurochem 70(1):242-51. [PubMed: 9422368]  [MGI Ref ID J:120242]

Suzuki M; Sugimoto Y; Ohsaki Y; Ueno M; Kato S; Kitamura Y; Hosokawa H; Davies JP; Ioannou YA; Vanier MT; Ohno K; Ninomiya H. 2007. Endosomal accumulation of Toll-like receptor 4 causes constitutive secretion of cytokines and activation of signal transducers and activators of transcription in Niemann-Pick disease type C (NPC) fibroblasts: a potential basis for glial cell activation in the NPC brain. J Neurosci 27(8):1879-91. [PubMed: 17314284]  [MGI Ref ID J:118352]

Takikita S; Fukuda T; Mohri I; Yagi T; Suzuki K. 2004. Perturbed myelination process of premyelinating oligodendrocyte in Niemann-Pick type C mouse. J Neuropathol Exp Neurol 63(6):660-73. [PubMed: 15217094]  [MGI Ref ID J:104958]

Taylor AM; Liu B; Mari Y; Liu B; Repa JJ. 2012. Cyclodextrin mediates rapid changes in lipid balance in Npc1-/- mice without carrying cholesterol through the bloodstream. J Lipid Res 53(11):2331-42. [PubMed: 22892156]  [MGI Ref ID J:190568]

Tokoro T; Yamamoto T; Nozaki K; Kusano K; Miyawaki S; Pentchev PG; Maekawa K; Eto Y. 1996. Allelic mutations in two Niemann-Pick disease model mice: SPM (C57BL/KSJ) and NCTR (NCTR-BALB/C) Jikeikai Med J 43:115-21.  [MGI Ref ID J:36039]

Treiber-Held S; Distl R; Meske V; Albert F; Ohm TG. 2003. Spatial and temporal distribution of intracellular free cholesterol in brains of a Niemann-Pick type C mouse model showing hyperphosphorylated tau protein. Implications for Alzheimer's disease. J Pathol 200(1):95-103. [PubMed: 12692847]  [MGI Ref ID J:149812]

Ulatowski L; Parker R; Davidson C; Yanjanin N; Kelley TJ; Corey D; Atkinson J; Porter F; Arai H; Walkley SU; Manor D. 2011. Altered vitamin E status in Niemann-Pick type C disease. J Lipid Res 52(7):1400-10. [PubMed: 21550990]  [MGI Ref ID J:174801]

Uronen RL; Lundmark P; Orho-Melander M; Jauhiainen M; Larsson K; Siegbahn A; Wallentin L; Zethelius B; Melander O; Syvanen AC; Ikonen E. 2010. Niemann-Pick C1 modulates hepatic triglyceride metabolism and its genetic variation contributes to serum triglyceride levels. Arterioscler Thromb Vasc Biol 30(8):1614-20. [PubMed: 20489167]  [MGI Ref ID J:179556]

Vainio S; Bykov I; Hermansson M; Jokitalo E; Somerharju P; Ikonen E. 2005. Defective insulin receptor activation and altered lipid rafts in Niemann-Pick type C disease hepatocytes. Biochem J 391(Pt 3):465-72. [PubMed: 15943586]  [MGI Ref ID J:117577]

Vazquez MC; del Pozo T; Robledo FA; Carrasco G; Pavez L; Olivares F; Gonzalez M; Zanlungo S. 2011. Alteration of gene expression profile in Niemann-Pick type C mice correlates with tissue damage and oxidative stress. PLoS One 6(12):e28777. [PubMed: 22216111]  [MGI Ref ID J:182335]

Veyron P; Mutin M; Touraine JL. 1996. Transplantation of fetal liver cells corrects accumulation of lipids in tissues and prevents fatal neuropathy in cholesterol-storage disease BALB/c mice. Transplantation 62(8):1039-45. [PubMed: 8900297]  [MGI Ref ID J:36923]

Wang MD; Franklin V; Sundaram M; Kiss RS; Ho K; Gallant M; Marcel YL. 2007. Differential regulation of ATP binding cassette protein A1 expression and ApoA-I lipidation by Niemann-Pick type C1 in murine hepatocytes and macrophages. J Biol Chem 282(31):22525-33. [PubMed: 17553802]  [MGI Ref ID J:124579]

Wang MD; Kiss RS; Franklin V; McBride HM; Whitman SC; Marcel YL. 2007. Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways. J Lipid Res 48(3):633-45. [PubMed: 17148552]  [MGI Ref ID J:120283]

Wasser CR; Ertunc M; Liu X; Kavalali ET. 2007. Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling. J Physiol 579(Pt 2):413-29. [PubMed: 17170046]  [MGI Ref ID J:140844]

Weintraub H; Abramovici A; Sandbank U; Pentchev PG; Brady RO; Sekine M; Suzuki A; Sela B. 1985. Neurological mutation characterized by dysmyelination in NCTR-Balb/C mouse with lysosomal lipid storage disease. J Neurochem 45(3):665-72. [PubMed: 4031853]  [MGI Ref ID J:7989]

Welch CL; Sun Y; Arey BJ; Lemaitre V; Sharma N; Ishibashi M; Sayers S; Li R; Gorelik A; Pleskac N; Collins-Fletcher K; Yasuda Y; Bromme D; D'Armiento JM; Ogletree ML; Tall AR. 2007. Spontaneous atherothrombosis and medial degradation in Apoe-/-, Npc1-/- mice. Circulation 116(21):2444-52. [PubMed: 17984379]  [MGI Ref ID J:142987]

Wu YP; Mizukami H; Matsuda J; Saito Y; Proia RL; Suzuki K. 2005. Apoptosis accompanied by up-regulation of TNF-alpha death pathway genes in the brain of Niemann-Pick type C disease. Mol Genet Metab 84(1):9-17. [PubMed: 15639190]  [MGI Ref ID J:95531]

Xie C; Burns DK; Turley SD; Dietschy JM. 2000. Cholesterol is sequestered in the brains of mice with Niemann-Pick type C disease but turnover is increased. J Neuropathol Exp Neurol 59(12):1106-17. [PubMed: 11138930]  [MGI Ref ID J:104996]

Xie C; Richardson JA; Turley SD; Dietschy JM. 2006. Cholesterol substrate pools and steroid hormone levels are normal in the face of mutational inactivation of NPC1 protein. J Lipid Res 47(5):953-63. [PubMed: 16461760]  [MGI Ref ID J:109000]

Xie C; Turley SD; Dietschy JM. 2000. Centripetal cholesterol flow from the extrahepatic organs through the liver is normal in mice with mutated niemann-pick type C protein (NPC1) J Lipid Res 41(8):1278-89. [PubMed: 10946016]  [MGI Ref ID J:64028]

Xie C; Turley SD; Dietschy JM. 1999. Cholesterol accumulation in tissues of the Niemann-pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ. Proc Natl Acad Sci U S A 96(21):11992-7. [PubMed: 10518564]  [MGI Ref ID J:76735]

Xie C; Turley SD; Pentchev PG; Dietschy JM. 1999. Cholesterol balance and metabolism in mice with loss of function of Niemann-Pick C protein. Am J Physiol 276(2 Pt 1):E336-44. [PubMed: 9950794]  [MGI Ref ID J:76733]

Xie X; Brown MS; Shelton JM; Richardson JA; Goldstein JL; Liang G. 2011. Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice. Proc Natl Acad Sci U S A 108(37):15330-5. [PubMed: 21896731]  [MGI Ref ID J:176587]

Xu S; Chen X; Wei X; Liu G; Wang Q. 2011. Presynaptic impairment in Niemann-Pick C1-deficient neurons: not dependent on presence of glial cells. Neurosci Lett 496(1):54-9. [PubMed: 21507342]  [MGI Ref ID J:173215]

Xu S; Zhou S; Xia D; Xia J; Chen G; Duan S; Luo J. 2010. Defects of synaptic vesicle turnover at excitatory and inhibitory synapses in Niemann-Pick C1-deficient neurons. Neuroscience 167(3):608-20. [PubMed: 20167265]  [MGI Ref ID J:161496]

Yadid G; Sotnik-Barkai I; Tornatore C; Baker-Cairns B; Harvey-White J; Pentchev PG; Goldin E. 1998. Neurochemical alterations in the cerebellum of a murine model of Niemann-Pick type C disease. Brain Res 799(2):250-6. [PubMed: 9675302]  [MGI Ref ID J:48956]

Yan X; Yang F; Lukas J; Witt M; Wree A; Rolfs A; Luo J. 2014. Hyperactive glial cells contribute to axonal pathologies in the spinal cord of Npc1 mutant mice. Glia 62(7):1024-40. [PubMed: 24644136]  [MGI Ref ID J:210979]

Yevenes LF; Klein A; Castro JF; Marin T; Leal N; Leighton F; Alvarez AR; Zanlungo S. 2012. Lysosomal vitamin E accumulation in Niemann-Pick type C disease. Biochim Biophys Acta 1822(2):150-60. [PubMed: 22120593]  [MGI Ref ID J:180321]

Yu T; Shakkottai VG; Chung C; Lieberman AP. 2011. Temporal and cell-specific deletion establishes that neuronal Npc1 deficiency is sufficient to mediate neurodegeneration. Hum Mol Genet 20(22):4440-51. [PubMed: 21856732]  [MGI Ref ID J:176888]

Yu W; Gong JS; Ko M; Garver WS; Yanagisawa K; Michikawa M. 2005. Altered cholesterol metabolism in Niemann-Pick type C1 mouse brains affects mitochondrial function. J Biol Chem 280(12):11731-9. [PubMed: 15644330]  [MGI Ref ID J:98011]

Yu W; Ko M; Yanagisawa K; Michikawa M. 2005. Neurodegeneration in heterozygous Niemann-Pick type C1 (NPC1) mouse: implication of heterozygous NPC1 mutations being a risk for tauopathy. J Biol Chem 280(29):27296-302. [PubMed: 15919659]  [MGI Ref ID J:100816]

Zhou S; Davidson C; McGlynn R; Stephney G; Dobrenis K; Vanier MT; Walkley SU. 2011. Endosomal/Lysosomal processing of gangliosides affects neuronal cholesterol sequestration in niemann-pick disease type C. Am J Pathol 179(2):890-902. [PubMed: 21708114]  [MGI Ref ID J:174399]

te Vruchte D; Lloyd-Evans E; Veldman RJ; Neville DC; Dwek RA; Platt FM; van Blitterswijk WJ; Sillence DJ. 2004. Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport. J Biol Chem 279(25):26167-75. [PubMed: 15078881]  [MGI Ref ID J:91039]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live FVB-congenic colony, heterozygous mice are bred with wildtype mice from the colony or with FVB/NJ inbred mice (Stock No. 001800).
Heterozygotes are viable and fertile. Homozygotes demonstrate progressive motor coordination deficits and survive a mean of 76 days. Heterozygous FVB background animals may breed earlier and for longer periods of time than the original BALB/cNctr background mice (see Stock No. 003092).

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


(6.8)