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Phenotypes Associated with This Genotype
Genotype
MGI:5642030
Allelic
Composition
Npc1tm1.1Dso/Npc1tm1.1Dso
Genetic
Background
B6.129-Npc1tm1.1Dso
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1tm1.1Dso mutation (0 available); any Npc1 mutation (17 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice have an average lifespan of 125 days; 59% longer than Npc1m1N homozygotes

growth/size/body
• lower body weight as compared to controls
• progressive weight loss beginning at 10 weeks of age

homeostasis/metabolism
• lipid storage in neocortex and liver
• lipid accumulation in P14 liver tissue includes: lactosylceramides, monohexosyceramides, sphingomyelins, sphingoid bases, gangiosides, unesterified cholesterol and 24(S)-hydroxycholesterol
• subcellular storage of cholesterol in lobule X Purkinje neurons in P63 mice
• cholesterol accumulation within cell bodies and axonal segments of neocortical neurons
• cholesterol storage appears in all layers of the necortex, in particular V and VI
• most metabolites localize to neuronal cell bodies
• abnormal accumulation in meganeurites
• cholesterol accumulation in hepatocytes and liver macrophages (CD68+)
• increase in unesterfied cholesterol in liver , but not brain, tissue of older mice
• accumulation of multiple sphingolipid species in liver and brain tissue of older mice, principally monohexosylceramides and lactosylceramides
• lipid accumulation in P14 liver tissue includes: lactosylceramides, monohexosyceramides
• subcellular storage of ganglioside GM2 in lobule X Purkinje neurons in P63 mice
• GM2 ganglioside accumulation within cell bodies and axonal segments of neocortical neurons
• GM2 and GM3 ganglioside accumulation is less than in Npc1m1N homozygotes
• ganglioside storage appears in all layers of the necortex, in particular V and VI
• most metabolites localize to neuronal cell bodies
• abnormal accumulation in meganeurites

behavior/neurological
• onset of resting tremor beginning at 8 weeks of age
• mice cannot maintain balance on rotating rod by 12 weeks of age

nervous system
• microglial pathology in molecular, Purkinje cell and granular cell layers
• progression and spatial pattern is delayed in comparison to Npc1m1N homozygotes
• age dependent increase in microglial activity
• subcellular storage of cholesterol in lobule X Purkinje neurons in P63 mice
• cholesterol accumulation within cell bodies and axonal segments of neocortical neurons
• cholesterol storage appears in all layers of the necortex, in particular V and VI
• most metabolites localize to neuronal cell bodies
• abnormal accumulation in meganeurites
• polymembranous storage bodies are found in lobule X Purkinje cells from P63 mice
• progressive, age-dependent Purkinje cell degeneration
• degree of loss is less severe at P63 than in Npc1m1N homozygotes
• 58% reduction of Purkinje cells at P63 in anterior cerebella; 91% reduction by P105
• 65% reduction of Purkinje cells at P105 in posterior cerebella
• 88% reduction of Purkinje cells at P105 in central cerebella
• 41% reduction of Purkinje cells at P105 in nodular cerebella
• no observable loss in lobule X at P105
• dystrophic dendritic abnormalities in cerebellar areas with Purkinje cell loss
• age dependent increase in astrocyte reactivity
• progression and spatial pattern is delayed in comparison to Npc1m1N homozygotes
• axonal spheroid formation in cerebellar areas with Purkinje cell loss

cellular
• liver macrophages exhibit a progressive foamy transformation

hematopoietic system
• polymembranous storage bodies found in liver macrophages
• increase in number of liver macrophages
• liver macrophages exhibit a progressive foamy transformation
• microglial pathology in molecular, Purkinje cell and granular cell layers
• progression and spatial pattern is delayed in comparison to Npc1m1N homozygotes
• age dependent increase in microglial activity

immune system
• polymembranous storage bodies found in liver macrophages
• increase in number of liver macrophages
• liver macrophages exhibit a progressive foamy transformation
• microglial pathology in molecular, Purkinje cell and granular cell layers
• progression and spatial pattern is delayed in comparison to Npc1m1N homozygotes
• age dependent increase in microglial activity

liver/biliary system
• cholesterol accumulation in hepatocytes and liver macrophages (CD68+)
• increase in unesterfied cholesterol in liver , but not brain, tissue of older mice
• polymembranous storage bodies found in hepatocytes

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Niemann-Pick disease DOID:14504 J:221855


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
10/08/2019
MGI 6.14
The Jackson Laboratory