Analysis Tools
mortality/aging
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• mutants have a maximum lifespan of 77 days, with mortality rate increasing drastically from 55 days onward
• mutants treated with 2-hydroxypropyl-beta-cyclodextrin (2-HPC) at P7 to lower cholesterol accumulation live significantly longer than saline-injected mutants, with a median survival of 103 days versus 69 days
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growth/size/body
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• mutants reach a maximum body weight of approximately 12 grams by 6 weeks of age which is about 30% less compared to controls
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weight loss
(
J:188345
)
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• weight declines progressively after 6 weeks of age until death
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behavior/neurological
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• mutants exhibit deficits in object memory index at 7 and 10 weeks of age; object recognition memory deficits are accelerated compared to single Npc1 homozygotes
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in cognitive performance
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• mutants exhibit impaired rotarod performance and gait coordination at 7 weeks of age which is further exacerbated by 10 weeks of age
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance
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• mutants exhibit reduced locomotor activity and increased periods of inactivity in open-field tests at both 7 and 10 weeks of age
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance
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nervous system
microgliosis
(
J:188345
)
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• mutants exhibit microglial activation in the hippocampus and cerebellum at a higher level than in single Npc1 homozygotes
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants
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• mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age
• however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls
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astrocytosis
(
J:188345
)
|
• mutants exhibit a profound increase in the number and activation of glial fibrillary acidic protein (GFAP)-labeled astrocytes in the hippocampus and cerebellum compared with wild-type, single Tg(PRNP-APPSweInd)8Dwst mutants, and single Npc1 homozygotes
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show decreased astrocyte activation compared to saline-injected mutants
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• neurodgeneration in the cerebellum is accelerated compared to single Npc1 homozygotes
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• decrease in the number of cerebellar Purkinje cells that is more pronounced than in single Npc1 homozygotes
• however neuronal loss in the hippocampus is not seen
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• mutants exhibit a loss of myelin fibre tracts in the hippocampus/cortex and cerebellum, indicating significant demyelination; demyelination is more severe than in single Npc1 homozygotes
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hematopoietic system
microgliosis
(
J:188345
)
|
• mutants exhibit microglial activation in the hippocampus and cerebellum at a higher level than in single Npc1 homozygotes
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants
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homeostasis/metabolism
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• cathepsin D levels are higher in the hippocampus and the cerebellum than in controls, including single Npc1 homozygotes
• cytosolic cathepsin D, cytochrome c and Bcl-2-associated X protein levels are increased in the cerebellum to a higher level than in single Npc1 homozygotes
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• mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age
• however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls
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• cathepsin D activity is higher in the hippocampus and the cerebellum than in controls, including single Npc1 homozygotes
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immune system
microgliosis
(
J:188345
)
|
• mutants exhibit microglial activation in the hippocampus and cerebellum at a higher level than in single Npc1 homozygotes
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Alzheimer's disease | DOID:10652 | J:188345 | ||
| Niemann-Pick disease | DOID:14504 | J:188345 | ||
