Mouse Genome Informatics
hm
    Npc2tm1Plob/Npc2tm1Plob
involves: 129S1/Sv * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Neurodegenerative changes affecting cerebullar Purkinje cells of Npc1m1N/Npc1m1N, Npc2tm1Plob/Npc2tm1Plob, and double homozygous mice for Npc1m1N and Npc2tm1Plob

mortality/aging
• all mice on a genetic background involving 129S1/Sv, BALB/c, C57BL/6 had died by ~130 days of age

behavior/neurological
• continuous tremor first detected at ~55 days of age
• following onset of tremors
• following onset of tremors

growth/size/body
• mice grew normally until ~55 days of age when they began to lose weight
• later onset and less progressive than in Npc1m1N homozygotes

homeostasis/metabolism
• 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
• 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
• similar progressive degeneration of loss as in Npc1m1 homozygotes, but later onset

liver/biliary system
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Niemann-Pick Disease, Type C1; NPC1 257220 J:89617