Mouse Genome Informatics
hm
    Npc1m1N/Npc1m1N
BALB/cNctr-Npc1m1N/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
nervous system
N
• unlike human Niemann-Pick Type C, neurofibrillary tangles are not found in the brain (J:149812)
• free cholesterol storage in neurons is found throughout the gigantocellular nucleus of the pons, but there is reduced cholesterol staining in the myelin sheaths of surrounding myelinated nerve fibers
• although CA1 does not have intracellular free cholesterol accumulation, by 3 weeks of age there is filipin staining material in almost every pyramidal neuron in CA3 and this increases at 5 and 10 weeks of age with extensive degeneration of CA3 neurons by 10 weeks of age
• accumulation of intracellular free cholesterol results in swollen neurons scattered throughout all neocortical layers; by 3 weeks of age, when clinical symptoms have not presented, there is accumulation of filipin staining in almost all neurons of the central cortex areas, cholesterol storage continues to increase, and by 10 weeks of age neuronal degeneration is found in the retrospinal cortex
• nearly all of the Purkinje cells are lost by 9 to 10 weeks of age (J:149812)
• pronounced loss of cerebellar Purkinje cells beginning at 6 weeks of age (J:179744)
• demyelination is observed in the corpus callosum, external capsule and internal capsule
• prepulse inhibition is blunted (45-55%) when compared to wild-type (60-65%)

cellular

homeostasis/metabolism
• 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
• esterified cholesterol in liver tissue decreases with age
• unesterified cholesterol in liver tissue increases with age

behavior/neurological
• mice exhibit an exaggerated response to stimuli (110 db) starting at 38-44 days of age
• first observed as a lateral displacement of each rear foot at 7 weeks of age
• decrease in motor capabilities as assessed by the inverted cage lid, coat hanger and balance beam tests
• first observed at 9 weeks of age

growth/size
• significant weight loss observed at 6-7 weeks of age as compared to controls

hematopoietic system
• difference in weight from wild-type becomes significant at 40 days of age, but is no longer significant at 60 days probably due to wasting

immune system
• difference in weight from wild-type becomes significant at 40 days of age, but is no longer significant at 60 days probably due to wasting

liver/biliary system
• esterified cholesterol in liver tissue decreases with age
• unesterified cholesterol in liver tissue increases with age

mortality/aging
• heterozygote matings produce less than the expected ratio of homozygotes (16-18% vs. 25%)
• average lifespan is 74 +/- 1.7 days

vision/eye
• corneal basal cells do not have distinguishable borders and cytoplasm
• corneas exhibit an increase in dendritic cell number
• corneas exhibit hyperreflective inclusions in intermediate and basal cells
• treatment with cyclodextrin/allopregnanolone results in regression of corneal inclusions

Mouse Models of Human Disease
OMIM IDRef(s)
Niemann-Pick Disease, Type C1; NPC1 257220 J:182268