mortality/aging
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• all mice are dead by 8 weeks postnatal
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• Background Sensitivity: in a mixed B6/CD-1 background, more embryos survive than on a B6 background, but only one third survive passed E13.5 and very few survive until 8 weeks postnatal
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growth/size/body
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• embryos found between E13.5 and E16.5 are small but morphologically normal
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• embryos have reduced body weight by about two-fold
• however, no visible behavioral or developmental defects are observed and all organ weights are proportional with the exception of the thymus and spleen
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nervous system
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• at E14.5, the cortical plate has threefold fewer migrating late born neurons and in a Boyden transwell assay cortical neurons fail to migrate in response to BDNF
• however, alignment and density of radial glial cells and the number of Cajal-Retzius neurons expressing Reelin are normal
• at E14.5 and E16.5, there is a decrease in cortical progenitor cell proliferation in the ventricular zone
• at E16.5, the distance between the subplate and the plial surface is reduced nearly two-fold (from 246um in controls to 127um) but the cortex width is reduced by only 16% (from 592um in controls to 497um in homozygotes)
• at E16.5, the clear boundary between the subplate and the intermediate zone, in which many neurons (TBB1+) are abnormally present, is not visible and cell density in the subplate and the intermediate zone is increased
• at E18.5, Pou3f2+ cells are located deeper in the cortical plate than in wild-type mice
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• at P19, neuronal cell bodies are small, round and nearly completely lack the pyramidal cell marker Pou3f2+ in the somatosensory and visual cortexes
• at P19, the more anterior cortex has reduced pyramidal cell marker expression (Pou3f2+)
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• at P19, the somatosensory cortex thickness is reduced in layers II, III and V
• however, there is an increase in cell number in layer IV
• at P19, neuronal cells nearly completely lack the pyramidal cell marker Pou3f2
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• at P19, mature neurons (NEUN+) are tightly packed in layers II and III unlike in wild-type
• at P19, the apical cortical dendrites (MAP2+) of layer II to V are unfasciculated and disorganized as determined
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• at P19, neuronal cells nearly completely lack the pyramidal cell marker Pou3f2
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• at P19, the somatosensory cortex thickness is reduced in layers II, III and V
• however, there is an increase in cell number in layer IV
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hematopoietic system
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• 10-fold lower
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• 10-fold lower
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embryo
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• embryos found between E13.5 and E16.5 are small but morphologically normal
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immune system
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• 10-fold lower
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• 10-fold lower
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endocrine/exocrine glands
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• 10-fold lower
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