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Phenotypes Associated with This Genotype
Genotype
MGI:5305070
Allelic
Composition
Npc1m1N/Npc1m1N
Genetic
Background
BALB/c-Npc1m1N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1m1N mutation (3 available); any Npc1 mutation (44 available)
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
• progression and spatial pattern is more advanced in comparison to Npc1tm1.1Dso homozygotes
• age dependent increase in microglial activity
• 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)
• focal axonal swellings are found in Purkinje cells of the cerebellar and vestibular nuclei, the granular layer, and the white matter tracts, an accumulation of vesicular storage material in the cytoplasm of the somata is evident beginning between 4 and 8 weeks of age, dendritic arbors and thick megadendrites are also found and Purkinje cell axonal swellings are common in the granule layer (J:81305)
• polymembranous storage bodies are found in lobule X Purkinje cells from P63 mice (J:221855)
• at 35 days of age Purkinje cell loss is not found, but by 45 days of age there is loss of zebrin II negative Purkinje cells throughout the cerebellum in a banded pattern which has bands of surviving Purkinje cells, but the posterior cerebellum only has some gaps in the molecular layer, especially in the hemispheres; at 60 days of age patterned Purkinje cell loss is clear in the posterior hemispheres and the anterior lobe of the cerebellum shows loss in bot the vermis and hemispheres, but the nodular zone and lobule X are resistant to this Purkinje cell loss. (J:81305)
• 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
• analysis at postnatal day 12 finds slightly fewer ACIII stained hippocampal neurons, indicative of fewer neurons having a primary cilium, and immuno-electron microscopy shows that these cilia are also shorter than those of wild-type controls
• 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
• progression and spatial pattern is more advanced in comparison to Npc1tm1.1Dso homozygotes
• age dependent increase in microglial activity

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

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

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Niemann-Pick disease DOID:14504 OMIM:257200
OMIM:257220
OMIM:607616
OMIM:607625
J:172769


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
02/13/2018
MGI 6.11
The Jackson Laboratory