nervous system
N |
• at E18.5, both male and female mice show no significant brain neuroanatomical phenotypes relative wild-type controls
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• in adult males, total brain area is significantly reduced by 7% at P45 and by 9% at P120 relative to wild-type males
• however, no significant differences are noted in male brain size at E18.5 and P10, or in female brain size at any of the time points assessed relative to sex-matched wild-type controls
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• at P120, the size of the male corpus callosum is smaller by 26% on parasagittal sections at lateral +0.60 mm relative to wild-type males
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• at P120, the size of the male thalamus is smaller by 24% on parasagittal sections at lateral +0.60 mm relative to wild-type males
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• at P120, males, but not females, exhibit small brain nuclei associated to the limbic system
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• at P120, the area of the male cingulate gyrus is reduced by 8% on coronal sections at bregma +0.98 mm relative to wild-type males; on parasagittal sections, the size of the cingulate gyrus is smaller by 25% at lateral +0.60 mm
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• at P120, the area of the male hippocampus is reduced by 24% on coronal sections at bregma -1.34 mm relative to wild-type males; on parasagittal sections, the size of hippocampus is also smaller by 24% at lateral +0.60 mm
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• at P120, the height of the male secondary somatosensory cortex is reduced by 12% at bregma +0.98 mm relative to wild-type males
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• at P120, the average cell area of neurons is significantly smaller in all affected male brain regions, including the cingulate gyrus (-15%) and the secondary somatosensory cortex (-15%)
• however, cell count is normal within each affected male brain region and cell size is unchanged in unaffected male brain regions (e.g. retrosplenial cortex)
• no defects in neuronal cell count or size are detected in female mice at P120
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• in culture, primary hippocampal neurons derived from E18.5 male embryos show a 6% reduction in the soma area along with a 23% reduction in growth cone area but no change in axonal length relative to wild-type neurons
• however, hippocampal neurons derived from female embryos show no morphological defects
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• pyramidal neurons of the male anterior cingulate gyrus exhibit a 5% reduction in the density of postsynaptic dendritic spines relative to wild-type neurons
• however, EM shows normal neuronal ultrastructure in the cingulate gyrus
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• pyramidal neurons of the male anterior cingulate gyrus exhibit a smaller mEPSC amplitude relative to wild-type neurons
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growth/size/body
microcephaly
(
J:343325
)
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• male microcephaly appears to be acquired between P10 and P45
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behavior/neurological
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• adult male mice show no major behavioral deficits in a broad range of behavioral tests evaluating anxiety, depression, anhedonia, memory, locomotion, coordination, motricity, sociability, schizophrenia, autism, and epilepsy
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