Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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nervous system
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• decreased brain amyloid-beta 40 and 42
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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nervous system
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• decreased brain amyloid-beta 40 and 42
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Npc1m1N mutation
(3 available);
any
Npc1 mutation
(72 available)
Tg(PRNP-APPSweInd)8Dwst mutation
(0 available)
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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 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
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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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• 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
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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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homeostasis/metabolism
immune system
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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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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Atp7btx-J mutation
(1 available);
any
Atp7b mutation
(82 available)
Tg(PRNP-APPSweInd)8Dwst mutation
(0 available)
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mortality/aging
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N |
• survival is increased compared to in Tg(PRNP-APPSweInd)8Dwst mice
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homeostasis/metabolism
nervous system
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• mice exhibit a 45% reduction in plaque area compared to in Tg(PRNP-APPSweInd)8Dwst mice due to a reduction in the number of plaques
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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nervous system
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• reduction in plaque formation compared to mice carrying just Tg(PRNP-APPSweInd)8Dwst
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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mortality/aging
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• Background Sensitivity: survival decreases to 25-40% within 120 days of life; only 17% (7/41) survive to 365 days
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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Increase in creatine deposits in hippocampus of Tg(PRNP-APPSweInd)8Dwst/0 mice with age
mortality/aging
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• Background Sensitivity: 20/52 mice die before 120 days, 3/52 by 130 days and 3/52 die after 250 days; 50% survive for at least a year
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behavior/neurological
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• mice show impairment in acquisition of spatial information during place discrimination training at 11 weeks of age; mice show longer latencies to reach escape platform and longer search paths to reach platform
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• during probe trial after completion of training, mice display lower annulus crossing index, searching for platform in a circular fashion and often crossing the centers of alternative quadrants, relative to non-transgenic controls
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nervous system
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N |
• no differences are seen in volume of dorsal hippocampus or in neuronal cytoarchitecture between transgenic and control mice
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• dense-cored amyloid deposits contain amyloid beta-42 peptide
(J:69967)
• 14-month old mutants show dense amyloid beta core plaques in the hippocampus
(J:166801)
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• by 101 days, plaques are detected within the pial vessels, and in the cerebral vasculature by 196 days
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• amyloid plaques are associated with dystrophic neurites; dystrophic neuron pathology increases with age and frequency of large cored plaques
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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mortality/aging
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• Background Sensitivity: survival decreases to 25-40% within 120 days of life; only 3/12 mice survive to 365 days
• survival is less than on other genetic backgrounds examined
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
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nervous system
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• observed at 16 and 20 weeks of age in hippocampus and cortex
• level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 16 weeks of age
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homeostasis/metabolism
Analysis Tools