behavior/neurological
| N |
• both male and female mice show normal exploratory and anxiety-like behaviors in the open field and elevated plus maze tests relative to wild-type controls
• both sexes show normal short-term spatial working memory in the Y-maze spontaneous alternation test as well as normal recognition memory in the novel object recognition test
• both sexes show normal grip strength at 1 year of age, with no changes observed in the same cohort of mice at 1.5 years of age, suggesting normal skeletal muscle function
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• transcriptomic analyses show altered gene expression and biological pathways in the cerebellum and motor cortex of female mice, likely contributing to the observed deficits in gross motor coordination and fine motor skills
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• at 19 months of age, both sexes show a significantly higher number of foot slips in an inclined beam walk task, with females displaying a more pronounced phenotype than males
• however, both sexes show improved performance (fewer foot slips) with successive trials, indicating normal motor learning
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• female, but not male, mice show a significantly shorter latency time to drop from an accelerating rotarod both at 1 year and at 1.5 years of age, indicating impaired motor coordination; female-specific motor phenotype does not worsen with age
• however, motor learning is intact in both sexes at 1 year of age and significantly improved in female, but not male, mice at 1.5 years of age
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• at 19 months of age, female mice show more pronounced deficits in fine motor skills than male mice in an inclined beam walk task
• when initially trained to run voluntarily on a normal training wheel with 38 rungs for 2 weeks, ~1.5-year-old female mice exhibit a significantly lower daily maximal running velocity, but no differences in distance traveled or average running velocity relative to wild-type controls
• strikingly, when switched over to a complex running wheel with 22 rungs missing in an alternate pattern, female, but not male, mice exhibit a significant decrease in daily maximal speed, distance traveled, and average running velocity
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cellular
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• female mice exhibit reduced expression of OXPHOS genes in the cerebellum relative to wild-type controls
• in contrast, OXPHOS transcripts are not significantly altered in the female motor cortex, where mitochondrial respiration is impaired
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• female mice show a significant reduction in mitochondrial respiration at complex CIV (cytochrome c oxidase) in the motor cortex, with no detectable changes in maximal oxygen consumption rate at complex I or complex II
• however, despite OXPHOS transcript downregulation in the cerebellum, female mice show no deficits in cerebellar mitochondrial respiration through CI, CII, or CIV
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growth/size/body
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IMPC - UCD
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hematopoietic system
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IMPC - UCD
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immune system
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IMPC - UCD
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nervous system
| N |
• both male and female mice (tested at 16 weeks and 39 weeks of age, respectively) show normal prepulse inhibition of the acoustic startle response relative to wild-type controls, indicating normal sensorimotor gating
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renal/urinary system
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IMPC - UCD
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IMPC - UCD
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reproductive system
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IMPC - UCD
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