mortality/aging
• although homozygotes develop normally through gastrulation, they fail to survive beyond E11
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embryo
• at E8.5, some mutant embryos appear unturned
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• as early as E8.5, mutant embryos appear developmentally retarded relative to wild-type embryos
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• at E8.0-E11.0, mutant embryos are significantly smaller than wild-type embryos
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• as early as E8.5, mutant embryos show prominent undulation of the neural tube
• however, the neural tube is closed
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cardiovascular system
dilated heart
(
J:72053
)
• at E8.0-E11.0, mutant embryos display a dilated heart filled with red blood cells
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• mutant embryos exhibit absence of a heartbeat, even at E11.0
• however, early mutant embryos can generate spontaneously contracting cardiomyocytes (not shown)
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nervous system
• as early as E8.5, mutant embryos show prominent undulation of the neural tube
• however, the neural tube is closed
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growth/size/body
• as early as E8.5, mutant embryos appear developmentally retarded relative to wild-type embryos
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• at E8.0-E11.0, mutant embryos are significantly smaller than wild-type embryos
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cellular
• although mutant fibroblast-like cells (FLCs) derived from ES cells can form prominent lamellipodia and filopodia in response to stimulation with serum or platelet-derived growth factor (PDGF), they show distinct defects in the actin-based motility of certain pathogens
• whereas the actin-based movement of the intracellular pathogen Listeria is largely normal, the motility of Shigella and vaccinia virus is severely blunted in mutant FLCs
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• unlike wild-type MEFs, fibroblasts isolated from E9.5 mutant embryos are initially viable but fail to expand
• in contrast, mutant FLCs derived from either ES cells or SV40-transformed embryos display normal growth rates relative to wild-type FLCs
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