FVB.C-Npc1^m1N/J

Stock number: 021755
Research areas: Internal/Organ Research, Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

This knockout allele of the Npc1 (Niemann Pick type C1) gene may be useful in studies of Niemann-Pick Type C disease.

Detailed description

This FVB/NJ congenic model of Niemann-Pick Type C disease was derived from backcrosses of the original Npc1^m1N (Niemann Pick type C1 NIH) spontaneous mutation strain (see Stock No. 003092), on the BALB/cNctr background.

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.

The Npc1^m1N allele is also available on a C57BL/6J congenic background (Stock No. 030097).

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.

Allele

Symbol: Npc1^m1N
Name: Niemann Pick type C1 NIH
MGI accession ID: MGI:1857409
Generation method: Spontaneous
Marker symbol: Npc1
Marker name: NPC intracellular cholesterol transporter 1
Chromosome: 18
Strain of origin: BALB/c
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.