Mouse Genome Informatics
hm
    Npc1m1N/Npc1m1N
BALB/c-Npc1m1N
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants start to die at 73 days of age (J:172769)
• average lifespan of approximately 80 days (J:221855)

growth/size/body
• mutants exhibit a progressive weight loss from 4 weeks of age

nervous system
• age dependent increase in microglial activity
• progression and spatial pattern is more advanced in comparison to Npc1tm1.1Dso homozygotes
• mutants exhibit vesicular accumulation of cholesterol in the cerebellum (J:172769)
• subcellular storage of cholesterol in lobule X Purkinje neurons in P63 mice (J:221855)
• cholesterol accumulation within cell bodies and axonal segments of neocortical neurons (J:221855)
• Background Sensitivity: decreased accumulation in P49 liver tissue as compared to C57BL/6 background, but level is higher than control (J:221855)
• polymembranous storage bodies are found in lobule X Purkinje cells from P63 mice
• lower number of surviving Purkinje cells in cerebellar lobes VIII and X (J:172769)
• progressive, age-dependent Purkinje cell degeneration (J:221855)
• degree of loss is more severe at P63 than in Npc1tm1.1Dso homozygotes (J:221855)
• increase in astrocytosis and microglia activation (J:172769)
• age dependent increase in astrocyte reactivity (J:221855)
• progression and spatial pattern is more advanced in comparison to Npc1tm1.1Dso homozygotes (J:221855)
• mutants exhibit demyelination in the white matter

behavior/neurological
• progressive decline in motor coordination after 4 weeks of age

homeostasis/metabolism
• Background Sensitivity: decreased lipid accumulation in P49 liver tissue as compared to C57BL/6 background
• lipids include: ceramides, monohexosyceramides, sphingomyelins, sphingoid bases, gangiosides, free cholesterol, 24(S)-hydroxycholesterol, 4beta-hydroxy cholesterol and cholesterol ester
• mutants exhibit vesicular accumulation of cholesterol in the cerebellum (J:172769)
• subcellular storage of cholesterol in lobule X Purkinje neurons in P63 mice (J:221855)
• cholesterol accumulation within cell bodies and axonal segments of neocortical neurons (J:221855)
• Background Sensitivity: decreased accumulation in P49 liver tissue as compared to C57BL/6 background, but level is higher than control (J:221855)
• cholesterol accumulation in hepatocytes and liver macrophages
• Background Sensitivity: decreased accumulation in P49 liver tissue as compared to C57BL/6 background
• Background Sensitivity: decreased accumulation in P49 liver tissue as compared to C57BL/6 background
• GM2 ganglioside accumulation within cell bodies and axonal segments of neocortical neurons
• GM2 and GM3 ganglioside accumulation is higher than in Npc1tm1.1Dso homozygotes
• subcellular storage of ganglioside GM2 in lobule X Purkinje neurons in P63 mice

cellular
• liver macrophages exhibit a progressive foamy transformation

hematopoietic system
• polymembranous storage bodies found in liver macrophages and hepatocytes
• liver macrophages exhibit a progressive foamy transformation
• age dependent increase in microglial activity
• progression and spatial pattern is more advanced in comparison to Npc1tm1.1Dso homozygotes

immune system
• polymembranous storage bodies found in liver macrophages and hepatocytes
• liver macrophages exhibit a progressive foamy transformation
• age dependent increase in microglial activity
• progression and spatial pattern is more advanced in comparison to Npc1tm1.1Dso homozygotes

liver/biliary system
• cholesterol accumulation in hepatocytes and liver macrophages
• polymembranous storage bodies found in liver macrophages and hepatocytes

Mouse Models of Human Disease
OMIM IDRef(s)
Niemann-Pick Disease, Type C1; NPC1 257220 J:172769