Analysis Tools
mortality/aging
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• although homozygous mutant embryos are present at normal Mendelian ratios at E9.5, only resorbed embryos are found at E10.5
• mid-gestational lethality is associated with a dramatic decrease in mtDNA content
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embryo
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• TUNEL staining of homozygous mutant embryos revealed massive apoptosis at E9.5, not observed in control littermates
• however, only a slight increase in TUNEL+ cells is noted at E8.5, indicating that loss of mitochondrial function leads to apoptosis
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• homozygous mutant embryos become growth arrested at E8.5
• however, no gross morphological defects are observed until E8.5
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• at E9.5, mutant embryos are significantly smaller than wild-type or heterozygous embryos
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cellular
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• at E9.5, some mitochondria resemble immature organelles
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• homozygous mutant embryos show a progressive decline in mtDNA content relative to wild-type embryos, already evident at E7.5
• at E7.5, E8.5 and E9.5, mutant mtDNA content is decreased to only 10%, 1% and 0.05% of wild-type, respectively, suggesting an association between embryonic lethality and loss of mtDNA
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• at E9.5, most mutant mitochondria show disorganized cristae
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• at E9.5, most mutant mitochondria appear enlarged and vacuolated
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• TUNEL staining of homozygous mutant embryos revealed massive apoptosis at E9.5, not observed in control littermates
• however, only a slight increase in TUNEL+ cells is noted at E8.5, indicating that loss of mitochondrial function leads to apoptosis
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• at E9.5, mutant embryos display severe mitochondrial dysfunction, as indicated by the absence of mitochondrial-encoded cytochrome c oxidase activity
• in contrast, the activity of succinate dehydrogenase remains unaffected
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growth/size/body
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• at E9.5, mutant embryos are significantly smaller than wild-type or heterozygous embryos
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