mortality/aging
• although born at normal Mendelian ratios, >20% of homozygotes die between 3 and 4 weeks of age, with a similar tendency for higher mortality thereafter
• most homozygotes die of unknown causes before 10 weeks after birth
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growth/size/body
• at 2 weeks of age, homozygotes are obviously smaller than wild-type controls
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• at 5 weeks of age, homozygotes weigh only ~50% of wild-type controls, and their body weight is similar to that of 2-week-old wild-type mice
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• although born at normal birth weight, homozygotes display significant weight reduction as they grow
• at 5 weeks of age, all organs examined are significantly smaller and lighter than those of wild-type controls
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behavior/neurological
• when the open field test is repeated 3 times every 24 hrs, the total distance of ambulation does not change significantly throughout the 3 tests, unlike in wild-type controls where the total distance of ambulation in the second test is significantly shorter than that in the first test
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• in the forced swim test, homozygotes display a significantly shorter immobility time than wild-type controls
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• in the open field test, homozygotes spend significantly more time in the central zone than wild-type controls, suggesting a reduced anxiety level
• in the elevated plus maze test, homozygotes spend a significantly longer time in the open arms and a shorter time in the central area than wild-type controls; no difference in the time spent in the closed arms
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• in the cliff-avoidance test, homozygotes show marked hyper-locomotion throughout the test session and peering down behavior; whereas >60% of wild-type controls remain on the platform after 7 min, all homozygotes peer down within 3 min, suggesting a higher impulsivity level
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• homozygotes frequently stand on their hindlegs and groom themselves with their forelegs in the resting time
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• in the open field test, the total distance of ambulation during 60 min is significantly greater than that of wild-type controls, suggesting a hyper-locomotive phenotype
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• when transferred to a cage where another mouse resides, a homozygote tends to spend a very long time following the resident mouse and constantly performs anogenital sniffing
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nervous system
• differentiation of neural stems cells to neural progenitor cells is impaired
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• more than 40% lighter than those of wild-type controls at 5 weeks of age
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• at 2 and at 20 weeks of age, mutant brains are smaller than wild-type
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• at 5 weeks of age
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• at E19.5, the mutant hippocampus appears poorly organized, unlike in wild-type controls
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• at E19.5, formation of the neuronal cell layers of the dentate gyrus is impaired in the hippocampus
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• at E19.5, the mutant dentate gyrus appears poorly organized, unlike in wild-type controls
• at 5 days and at 5 weeks of age, the number of cells in dentate gyrus is significantly decreased relative to that in wild-type controls
• at 5 weeks of age, the number of Sox1+ neural progenitor cells in the dentate gyrus is decreased relative to that in wild-type controls
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• at E19.5, the number of cells in the neuronal cell layer is smaller in homozygous mutant embryo than in wild-type embryos
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• at 5 days of age, the number of granular neurons in the mutant dentate gyrus is smaller than that in wild-type controls
• at 5 weeks of age, the number of granular neurons in the mutant dentate gyrus is reduced, and the border of the granular cell layer is indistinct relative to that in wild-type controls
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• at 5 weeks of age, the number of Sox1+ neural progenitor cells in the cerebellum is decreased relative to that in wild-type controls
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• at 5 weeks of age, homozygotes display fewer Sox1+ neural progenitor cells in the dentate gyrus and cerebellum than wild-type controls
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• differentiation of neural stems cells to neural progenitor cells is impaired
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• homozygotes exhibit significantly reduced prepulse inhibition scores at 69 dB and 73 dB relative to wild-type controls
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skeleton
• at 5 weeks of age, homozygotes show a 54% reduction in the thickness of the femoral growth plate relative to wild-type controls
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cellular
• differentiation of neural stems cells to neural progenitor cells is impaired
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endocrine/exocrine glands
• more than 40% lighter than those of wild-type controls at 5 weeks of age
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• more than 40% lighter than those of wild-type controls at 5 weeks of age
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• more than 40% lighter than those of wild-type controls at 5 weeks of age
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hematopoietic system
• more than 40% lighter than those of wild-type controls at 5 weeks of age
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• more than 40% lighter than those of wild-type controls at 5 weeks of age
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immune system
• more than 40% lighter than those of wild-type controls at 5 weeks of age
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• more than 40% lighter than those of wild-type controls at 5 weeks of age
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cardiovascular system
• less than 30% lighter than those of wild-type controls at 5 weeks of age
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liver/biliary system
• at 5 weeks of age
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renal/urinary system
• less than 30% lighter than those of wild-type controls at 5 weeks of age
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respiratory system
• at 5 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
schizophrenia | DOID:5419 |
OMIM:181500 |
J:214267 |