Mouse Genome Informatics
hm
    Npc1nmf164/Npc1nmf164
C57BL/6J-Npc1nmf164/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
behavior/neurological
• mice exhibit an exaggerated response to stimuli (110 db) starting at 55-60 days of age
• decrease in motor capabilities as assessed by the inverted cage lid, coat hanger and balance beam tests
• first observed at 11 weeks of age
• mice show an unsteady gait detectable between 4 and 12 weeks of age

reproductive system
• mutants do not breed well

cellular
• mice exhibit an accumulation of foamy macrophages in the lungs, but no alveolar proteinosis
• progressive accumulation of sphingomyelin in liver

growth/size
• weight loss observed at 9-10 weeks of age as compared to controls

hematopoietic system
• mice exhibit an accumulation of foamy macrophages in the lungs, but no alveolar proteinosis
• difference in weight from wild-type becomes significant at 90 days of age
• increase in microglial cell activation in the cerebellum

homeostasis/metabolism
• Lysobisphosphatidic acid (LBPA) and glycosylceramide levels are increased in liver
• lipid accumulation in vacuole-like inclusions is observed in liver and spleen by 60 days of age
• GM2 levels are very high in the brain by 15 days of age and remain elevated
• GM3 levels begin to increase by 15 days of age and rise progressively until at least 90 days
• liver tissue contains large amounts of gangliosides (GM2 and GM3)
• progressive accumulation of sphingomyelin in liver
• cholesterol levels are increased in the neuronal cell bodies of the CA3 region of the hippocampus, cortex, and Purkinje cells
• esterified cholesterol in liver tissue is 3-10 fold lower than controls and decreases with age
• unesterified cholesterol in liver tissue increases with age and is 10-20 fold higher than controls at older ages

immune system
• mice exhibit an accumulation of foamy macrophages in the lungs, but no alveolar proteinosis
• difference in weight from wild-type becomes significant at 90 days of age
• increase in microglial cell activation in the cerebellum

liver/biliary system
• esterified cholesterol in liver tissue is 3-10 fold lower than controls and decreases with age
• unesterified cholesterol in liver tissue increases with age and is 10-20 fold higher than controls at older ages

mortality/aging
• heterozygote matings produce less than the expected ratio of homozygotes
• average lifespan is 112 +/- 4 days

nervous system
• increase in microglial cell activation in the cerebellum
• cholesterol levels are increased in the neuronal cell bodies of the CA3 region of the hippocampus, cortex, and Purkinje cells
• loss of cerebellar Purkinje cells is first observed at P30; by P90 few cells are left
• increase in astrocyte activation in the cerebellum
• prepulse inhibition is blunted (30%) when compared to wild-type (40%)

Mouse Models of Human Disease
OMIM IDRef(s)
Niemann-Pick Disease, Type C1; NPC1 257220 J:179744