This knockout allele of the Npc1 (Niemann Pick type C1) gene may be useful in studies of Niemann-Pick Type C disease.
Dr. Matthew Scott, Stanford University School of Medicine
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), 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 Npc1m1N allele is also available on a C57BL/6J congenic background (Stock No. 030097).
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 Name||Niemann Pick type C1 NIH|
|Allele Synonym(s)||-npc; CSD; lcsd; lysosomal cholesterol storage disease; nctr; NPC; Npc-; npcnih; NPC1; NPC1-; Npc1N; npc1NIH|
|Gene Symbol and Name||Npc1, NPC intracellular cholesterol transporter 1|
|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.|
When 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).
When using the FVB.C-Npc1m1N/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021755 in your Materials and Methods section.