Analysis Tools
mortality/aging
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• mutants exhibit a reduced lifespan with only 30% of mice living past 90 days
• 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 107 days versus 85 days
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behavior/neurological
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• mutants exhibit deficits in object memory index at 10 weeks of age, but not at 7 weeks of age, on the object recognition memory test
• 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 10 weeks of age but not at 4 or 7 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 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
)
|
• mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
• 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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• neurodgeneration in the cerebellum
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• decrease in the number of cerebellar Purkinje cells; cell loss is less pronounced than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
• however neuronal loss in the hippocampus is not seen
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show decreased Purkinje cell loss compared to saline-injected mutants
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• mutants exhibit demyelination in the hippocampus/cortex and cerebellum, however demyelination is less severe than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants at earlier stages
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hematopoietic system
microgliosis
(
J:188345
)
|
• mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
• 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 and activity are higher in the hippocampus and the cerebellum than in controls, although this is lower than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
• cytosolic cathepsin D, cytochrome c and Bcl-2-associated X protein levels are increased in the cerebellum although to a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst 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
|
immune system
microgliosis
(
J:188345
)
|
• mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Niemann-Pick disease | DOID:14504 | J:188345 | ||
