Description

Strain Information

Former Names BALB/cNctr-Npc1N/+    (Changed: 15-DEC-04 ) Type Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Generation ?+F22 (13-NOV-08)

Appearance
albino, ataxic, tremors
Related Genotype: a/a Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c Npc1^m1N/Npc1^m1N

albino, unaffected
Related Genotype: a/a Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c Npc1^m1N/+ or +/+

Description
Mice homozygous for the recessive NIH allele of the Niemann Pick type C1 gene (Npc1^m1N) show a dual deficiency of sphingomyelinase and glucocerebrosidase activity. The overall phenotype resembles the sphingomyelinosis condition seen in mice homozygous for the sphingomyelinosis allele (Npc1^spm, Stock No. 002760). Sphingomyelinosis mutant mice begin to lose weight and to show tremor and ataxic gait at about 7 weeks of age. Weight loss continues and tremor and ataxia become more severe until death at about 12 to 14 weeks of age. The liver and spleen are also enlarged and Purkinje cells in the cerebellum are severely depleted. Sphingomyelin and free cholesterol are markedly elevated in liver and spleen but not in brain. Sphingomyelinosis closely resembles that of human Niemann-Pick Type C disease patients.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Npc1

004817	C57BL/6J-Npc1nmf164/J
002760	C57BLKS/J-Npc1spm/J

View Strains carrying other alleles of Npc1     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Niemann-Pick Disease, Type C1; NPC1 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Npc1^m1N/Npc1^m1N

        involves: BALB/c

• life span-post-weaning/aging
• premature death (MGI Ref ID J:81305)
  • ~75 day life span
• behavior/neurological phenotype
• abnormal eating behavior (MGI Ref ID J:76733)
  • poor food intake, beginning at 7 weeks of age
• abnormal motor capabilities/coordination/movement (MGI Ref ID J:76733)
  • defects beginning at 7 to 8 weeks of age
• growth/size phenotype
• weight loss (MGI Ref ID J:76733)
  • beginning at 7 to 8 weeks of age
• hematopoietic system phenotype
• enlarged spleen (MGI Ref ID J:76733)
  • progressive splenomegaly, beginning at 7 weeks of age
• homeostasis/metabolism phenotype
• abnormal cellular cholesterol metabolism (MGI Ref ID J:104996)
  • higher rate of turnover although whole body pool is considerably elevated
  • rate of cholesterol synthesis is reduced
• abnormal lipid homeostasis (MGI Ref ID J:18511)
  • lipid accumulation (including sphingomyelin, glucocerebroside, lactosylceramide, and cholesterol) in various organs including the liver, lung, kidney, thymus, spleen, and brain
• abnormal circulating cholesterol level (MGI Ref ID J:18511)
  • progressively increasing plasma cholesterol levels
• decreased cholesterol level (MGI Ref ID J:104996)
  • decreased levels in the brain at 7 weeks of age relative to controls
• increased cholesterol level (MGI Ref ID J:104996)
  • elevated in most organs except the brain at 7 weeks of age
  • elevated in the brain at 1 day of age
• immune system phenotype
• enlarged spleen (MGI Ref ID J:76733)
  • progressive splenomegaly, beginning at 7 weeks of age
• liver/biliary system phenotype
• increased liver weight (MGI Ref ID J:76733)
  • progressive increase in liver weight, beginning at 7 weeks of age
• reproductive system phenotype
• infertility (MGI Ref ID J:76395)
  • females showed normal oogenesis, but lacked implantation sites after successful plugging
• respiratory system phenotype
• increased lung weight (MGI Ref ID J:76733)
  • progressive increase in lung weight, beginning at 7 weeks of age
• nervous system phenotype
• abnormal anterior vermis (MGI Ref ID J:81305)
  • by P45, Purkinje cell loss was most evident in the anterior cerebellar vermis
  • degenerating cells belonged preferentially to the zebrin II-negative subtype
• abnormal myelination (MGI Ref ID J:104996)
  • reduced levels of both myelin protein and myelin cholesterol
• abnormal neuron morphology (MGI Ref ID J:104996)
  • vacuolated cytoplasmic storage material in all regions of the central nervous system
• Purkinje cell degeneration (MGI Ref ID J:81305)
  • localized axonal swellings, malformations of the dendritic arbor, and accumulation of vesicular storage materials within the cytoplasm
• decreased Purkinje cell number (MGI Ref ID J:81305)
  • 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
• abnormal posterior vermis (MGI Ref ID J:81305)
  • by P45, some Purkinje cell loss was evident in the posterior cerebellar vermis
  • at P60, most surviving Purkinje cells were located in the posterior vermis
• decreased brain weight (MGI Ref ID J:76733)
  • progressive decrease in brain weight, beginning at 7 weeks of age
• cellular phenotype
• abnormal cellular cholesterol metabolism (MGI Ref ID J:104996)
  • higher rate of turnover although whole body pool is considerably elevated
  • rate of cholesterol synthesis is reduced

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Npc1^m1N/Npc1^m1N

        involves: 129S1/Sv * BALB/c * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:89617)
  • all mice on a genetic background involving 129S1/Sv, C57BL/6, and BALB/c died by ~120 days of age
• growth/size phenotype
• weight loss (MGI Ref ID J:89617)
  • earlier onset and faster progression than in Npc2^tm1Plob homozygotes
• homeostasis/metabolism phenotype
• abnormal lipid homeostasis (MGI Ref ID J:89617)
  • 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
  • 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
  • galactosylceramide levels were reduced in the brain, reflecting a general loss of myelin lipids
• increased cholesterol level (MGI Ref ID J:89617)
  • about a 6 fold increase in total cholesterol accumulation in the liver at 28 days of age
  • about a 10 fold increase in total cholesterol accumulation in the liver at 50 days of age
  • 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
  • on the cellular level in the brain, unesterified cholesterol was stored in neurons within the neocortex, dentate gyrus, hippocampus, and cerebellum
• nervous system phenotype
• Purkinje cell degeneration (MGI Ref ID J:89617)

Npc1^m1N/Npc1^m1N

        involves: 129S2/SvPas * BALB/c * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:118352)
  • lifespan of Npc1-null mice expressing Il6 is modestly reduced compared to double null littermates

View Research Applications

Research Applications

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

Npc1^m1N related

Internal/Organ Research
Liver Defects
Spleen Defects

Metabolism Research

Mouse/Human Gene Homologs
Niemann-Pick disease, type C

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

Genes & Alleles

Gene & Allele Information

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 Origin		BALB/c
Gene Symbol and Name		Npc1, Niemann Pick type C1
Chromosome		18
Gene Common Name(s)		A430089E03Rik; C85354; 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^m1N, SEP PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

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]

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]

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]

Miyawaki S; Mitsuoka S; Sakiyama T; Kitagawa T. 1982. Sphingomyelinosis, a new mutation in the mouse: a model of Niemann-Pick disease in humans. J Hered 73(4):257-63. [PubMed: 7202025]  [MGI Ref ID J:6833]

Miyawaki S; Mitsuoka S; Sakiyama T; Kitagawa T. 1983. Time course of hepatic lipids accumulation in a strain of mice with an inherited deficiency of sphingomyelinase. J Hered 74(6):465-8. [PubMed: 6315811]  [MGI Ref ID J:7245]

Miyawaki S; Yoshida H; Mitsuoka S; Enomoto H; Ikehara S. 1986. A mouse model for Niemann-Pick disease. Influence of genetic background on disease expression in spm/spm mice. J Hered 77(6):379-84. [PubMed: 3559164]  [MGI Ref ID J:8630]

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]

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]

Npc1^m1N related

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]

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]

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]

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]

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; 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]

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]

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]

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]

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]

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]

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]

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; 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; 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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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]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Mating System	Heterozygote x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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      JAX^® Mice Orders
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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.