growth/size/body
microcephaly
(
J:224504
)
• dwarfism at birth that remains throughout adulthood
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• embryos show growth retardation at E17.5 but not at E15.5
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nervous system
• reduction of neurons in layers II-VI of the P2 cerebral cortex, with most pronounced thinning of the later-born superficial cortical layers
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• thinning of the cerebral cortex is seen at E17.5 and is more pronounced at P2
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• decrease in the numbers of Pax6+ neural progenitor cells and Tbr2+ intermediate neural progenitors at E15.5 and E17.5
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• increase in cell death of neural progenitor cells and intermediate neural progenitors, but not of differentiated neurons at E15.5 and E17.5
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reproductive system
cellular
• neural progenitor cells show mitotic arrest in the M phase
• increase in the number of MEFs arrested in mitosis, mainly in prometaphase and metaphase
• a number of MEFs exhibit delayed mitotic progression and subsequently die during mitosis and a number of cells abort cell division
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• the kinetochore-associated checkpoint protein Mad2 remains present on the kinetochores of MEFs in metaphase, including on unaligned chromosomes
• greater than 4-fold increase in mitotic cells with unaligned or lagging chromosomes
• MEFs show defective microtubule-kinetochore attachment and tension across sister kinetochores, leading to the activation of the spindle checkpoint
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• a small number of mutant mitotic MEFs exhibit aberrant spindles with reduced microtubule density
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• increase in the sub-G0 (less than 2N) population in MEFs, suggesting cell death
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