These mice carry an ENU-induced mutation characterized by ataxia, sphingomyelinosis, and abnormal cholesterol levels in liver. Degeneration of the purkinje cell layer in the cerebellum is also seen.
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Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Chemically induced (ENU) (Hypomorph) | Npc1 | NPC intracellular cholesterol transporter 1 |
Npc1 is a transmembrane protein involved in endosomal lipid sorting and trafficking. The nmf164 allele is a point mutation, which results in partial functional loss of the protein. In comparison to mice carrying Npc1spm (Stock #002760) and Npc1m1N (Stock #003092), the nmf164 phenotype has a delayed onset and models a more slowly progressing form of human Niemann-Pick C disease. Mice exhibit age-dependent ataxia, impaired motor and strength capabilities, shortened lifespan (112 +/- 4 days), weight loss, progressive accumulation of sphingomyelin and glycosphingolipids in the liver and spleen (sphingomyelinosis), and abnormal cholesterol levels in liver. In the brain, phenotypic characteristics include: loss of cerebellar Purkinje cells, an increase in the GM2 and GM3 gangliosides, abnormal astrocyte and microglial cell activation, abnormal cholesterol levels in neurons, and acoustic startle response abnormalities. This mutant mouse strain may be useful in studies of Niemann-Pick C disease.
Standard pathology work-up on two mutants (91 or 104 days of age) showed degeneration of the purkinje cell layer in the cerebellum. Lysosomal storage of lipid was also noted in macrophages present in the liver and spleen, as well as in the cytoplasm of neurons in the cerebral cortex. Apoptosis of the inner portion of the inner nuclear layer of the retina, and atrophic seminiferous tubules were also noted in one mutant.
This phenotypic deviant was identified following multidose ethylnitrosourea (ENU) treatments to induce mutations in male founder C57BL/6J mice during a forward genetic screen for recessive neurological phenotypes at the Neuroscience Mutagenesis Facility at The Jackson Laboratory. Mutagenized males were outcrossed to C57BL/6J females. The mutation results in a A to G transversion in exon 20 of 25 exons. The mutation alters the corresponding amino acid from aspartate to glycine at codon 1005 (D1005G) in loop I of the protein between the eighth and ninth (of 13) transmembrane domains.
Allele Name | neuroscience mutagenesis facility, 164 |
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Allele Type | Chemically induced (ENU) (Hypomorph) |
Allele Synonym(s) | Npc1spm-J; sphingomyelinosis Jackson |
Gene Symbol and Name | Npc1, NPC intracellular cholesterol transporter 1 |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 18 |
Molecular Note | This phenotypic mutant was identified in an ENU mutagenesis screen. A noncomplementation test with other Npc1 alleles showed that nmf164 represents an allele of Npc1. The mutation is an A to G transversion at coding nucleoide 3014 (c.3014A>G) in exon 20 of 25 exons, altering the corresponding amino acid from aspartate to glycine at codon 1005 (p.D1005G) in loop I of the protein between the eighth and ninth (of 13) transmembrane domains. Western blot analysis reveals that protein levels reduced to 10-15% of wild type. |
When using the C57BL/6J-Npc1nmf164/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004817 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Wildtype and Heterozygous for Npc1<nmf164> |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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