mortality/aging
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• no viable embryos are recovered at E6.5, E7.5, or E8.5
• examination of isolated decidual tissues indicate that embryos successfully implant but fail to progress beyond the egg cylinder stage
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embryo
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• elevated levels of caspase-3 in embryos at E5.0
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• decreased proliferation coinciding with an increase in gamma H2AX foci indicating premature senescence
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• fail to progress beyond the egg cylinder stage
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• at E5.5
• at E5.0 the total number of cells in all three lineages (epiblast, visceral endoderm, and extraembryonic ectoderm) is reduced
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cellular
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• blockade in autophagic flux
• following infection with a reporter adenovirus embryos show an increase in autophagosomes
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• elevated levels of caspase-3 in embryos at E5.0
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• in embryos at E5.0
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• decreased proliferation coinciding with an increase in gamma H2AX foci indicating premature senescence
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• in the epiblast at E5.0
• premature senescence is seen in visceral endoderm and extraembryonic ectoderm
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• impaired acidification indicated by elevated pH and reduced proteolytic activity
• reduction of lysosomal pH rescues premature senescence and extend survival of embryos by 2 days
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homeostasis/metabolism
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• blockade in autophagic flux
• following infection with a reporter adenovirus embryos show an increase in autophagosomes
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growth/size/body
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• at E5.5
• at E5.0 the total number of cells in all three lineages (epiblast, visceral endoderm, and extraembryonic ectoderm) is reduced
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Analysis Tools