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 Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +F12N8F1pN1

Appearance
black, ataxic, tremors
Related Genotype: a/a Npc1^spm/Npc1^spm

black, unaffected
Related Genotype: a/a Npc1^spm/+ or a/a ?/+

Description
The sphingomyelinosis mutation (Npc1^spm) arose in the C57BLKS inbred strain. Homozygous 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. A dual deficiency of sphingomyelinase and glucocerebrosidase activity has been described in BALB/c mice (npc1^N) with resemblance to the sphingomyelinosis condition.

Control Information

	Control
	Untyped from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Npc1

003092	BALB/cNctr-Npc1m1N/J
004817	C57BL/6J-Npc1nmf164/J

View Strains carrying other alleles of Npc1     (2 strains)

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Npc1^spm 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

Currently there is no phenotype information for this strain.

Genes & Alleles

Gene & Allele Information

Allele Symbol		Npc1spm
Allele Name		sphingomyelinosis
Allele Type		Spontaneous
Common Name(s)		spm;
Strain of Origin		C57BLKS/J
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;
General Note		On the C57BLKS background, homozygotes 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 (J:6833). Enlargement of liver and spleen is present as early as 4 weeks of age on the C57BLKS background although it does not occur on some other backgrounds (J:7245, J:8630). Large areas of liver and spleen are replaced by foam cells. Purkinje cells in the cerebellum are severely depleted. Sphingomyelin and free cholesterol are markedly elevated in liver and spleen but not in brain. Sphingomyelinase activity is reduced by 70% in liver, 50% in spleen, and 20% to 30% in brain. Altered levels of sphingomyelin, cholesterol, andsphingomyelinase are present in liver from 4 weeks of age onward. Hepatosplenomegaly appears as early as 4 weeks of age (J:7245). Heterozygotes have normal lipid concentrations and sphingomyelinase activity (J:6833). Sphingomyelinosis in Npc1spm homozygotes closely resembles that of human Niemann-Pick disease patients (J:8630). Cell lines derived from these embryos exhibit accumulation of intracellular cholesterol, attenuated esterification of exogenously added cholesterol, and increased de novo synthesis, as compared to cell lines from heterozygous embryos. The abnormalities are similar to those observed in fibroblasts from patients with Niemann-Pick disease type C (J:3691). The Npc1spm mutation maps to Chr 18 in intersubspecific (J:3259) and intraspecific backcrosses (J:39614). The Smpd1 gene that encodes acid sphingomyelinase in the mouse maps to mouse Chr 7 in somatic cell hybrids (J:15622). There are no mutations of the Smpd1 gene in sphingomyelinosis mutant mice (J:15622). Human Niemann-Pick type C gene maps to Chr 18 in a region conserved in mouse Chr 18 (J:4347). A dual deficiency of sphingomyelinase and glucocerebrosidase activity has been described in BALB/c mice with resemblance to the Npc1spm condition (J:18511). The defect in BALB/c mice does not involve a mutation in Smpd1 . Thus, Npc1spm and the BALB/c defect are models for type C Niemann-Pick disease, with reduced sphingomyelinase activity secondary to a cholesterol transport abnormality (J:41469).

Genotyping

Genotyping Information

Genotyping Protocols

Npc1^spm, PYRO, vers. 2
Npc1^spm, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

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]

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]

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]

Npc1^spm related

Akaboshi S; Yano T; Miyawaki S; Ohno K; Takeshita K. 1997. A C57BL/KsJ mouse model of Niemann-Pick disease (spm) belongs to the same complementation group as the major childhood type of Niemann-Pick disease type C. Hum Genet 99(3):350-3. [PubMed: 9050921]  [MGI Ref ID J:38800]

Cho SK; Gao N; Pearce DA; Lehrman MA; Hofmann SL. 2005. Characterization of lipid-linked oligosaccharide accumulation in mouse models of Batten disease. Glycobiology 15(6):637-48. [PubMed: 15647513]  [MGI Ref ID J:112499]

Erickson RP; Aviles RA; Zhang J; Kozloski MA; Garver WS; Heidenreich RA. 1997. High-resolution mapping of the spm (Niemann-Pick Type C) locus on mouse chromosome 18. Mamm Genome 8(5):355-6. [PubMed: 9107683]  [MGI Ref ID J:39614]

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]

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]

Ohno K; Nanba E; Miyawaki S; Sakiyama T; Kitagawa T; Takeshita K. 1992. A cell line derived from sphingomyelinosis mouse shows alterations in intracellular cholesterol metabolism similar to those in type C Niemann-Pick disease. Cell Struct Funct 17(4):229-35. [PubMed: 1394466]  [MGI Ref ID J:3691]

Sakai Y; Miyawaki S; Shimizu A; Ohno K; Watanabe T. 1991. A molecular genetic linkage map of mouse chromosome 18, including spm, Grl-1, Fim-2/c-fms, and Mbp. Biochem Genet 29(1-2):103-13. [PubMed: 1679325]  [MGI Ref ID J:3259]

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]

Tokoro T; Yamamoto T; Kusanno K; Miyawaki S; Eto Y. 1991. Impaired exogenous cholesterol esterification in Niemann-Pick mouse Am J Hum Genet 49(4 Suppl):107 (Abstr.).  [MGI Ref ID J:685]

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]

Yamada A; Saji M; Ukita Y; Shinoda Y; Taniguchi M; Higaki K; Ninomiya H; Ohno K. 2001. Progressive neuronal loss in the ventral posterior lateral and medial nuclei of thalamus in Niemann-Pick disease type C mouse brain. Brain Dev 23(5):288-97. [PubMed: 11504598]  [MGI Ref ID J:102782]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. 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
	Untyped 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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