Phenotypes Associated with This Genotype

Genotype
MGI:3044831

• Allelic Composition: Npc1^m1N/Npc1^m1N
• Genetic Background: involves: 129S1/Sv * BALB/c * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Neurodegenerative changes affecting cerebullar Purkinje cells of Npc1^m1N/Npc1^m1N, Npc2^tm1Plob/Npc2^tm1Plob, and double homozygous mice for Npc1^m1N and Npc2^tm1Plob

mortality/aging

premature death ( J:89617 )

• all mice on a genetic background involving 129S1/Sv, C57BL/6, and BALB/c died by ~120 days of age

growth/size/body

weight loss ( J:89617 )

• earlier onset and faster progression than in Npc2^tm1Plob homozygotes

homeostasis/metabolism

abnormal lipid homeostasis ( J:89617 )

• 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

increased liver cholesterol level ( J:89617 )

• 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

Purkinje cell degeneration ( J:89617 )

liver/biliary system

increased liver cholesterol level ( J:89617 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Niemann-Pick disease		DOID:14504		J:89617