mortality/aging
embryonic lethality between implantation and placentation, complete penetrance
(
J:290315
, J:279207
)
• although homozygous embryos are recovered at expected Mendelian ratios at E7.5, decidua with embryo resorptions are detected at E8.5
(J:290315)
• homozygous embryos are recovered in expected Mendelian ratios at E7.5 but arrest prior to gastrulation; no homozygous embryos are recovered at E9.5
(J:279207)
|
embryo
• no structures typical of gastrulation are observed at E7.5
(J:290315)
• no hallmarks typical of gastrulating embryos are observed at E7.5
(J:279207)
|
• embryos stall at about the size of wild-type E6.0 embryos, just prior to the onset of gastrulation; only two cell layers with bilaterally symmetric egg-cylinder morphology are seen at E7.5
(J:290315)
• however, no disorganization or pyknotic/dying cells are apparent at E7.5
(J:290315)
• embryos arrest prior to gastrulation
(J:279207)
|
• at E7.5, embryos are significantly delayed and appear as relatively pristine early egg-cylinder stage embryos
• however, no widespread active Trp53-positive apoptotic cells are detected at E7.5
|
• at E7.5, embryos are dramatically smaller than controls
(J:290315)
• embryos are much smaller than controls at E7.5
(J:279207)
|
• at E7.5, embryos still retain robust nuclear Pou5f/Oct4 signal in the epiblast
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• a rudimentary egg cylinder is observed at E7.5
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• no morphological head folds are evident at E7.5
(J:290315)
• no head folds are present at E7.5
(J:279207)
|
• no morphological nodes are evident at E7.5
(J:290315)
• no embryonic node is present at E7.5
(J:279207)
|
• no morphological primitive streak or Brachyury (T)-positive cells are detected at E7.5
(J:290315)
• no morphological evidence of primitive streak formation is observed at E7.5
(J:279207)
|
• no morphological allantois is evident at E7.5
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growth/size/body
• at E7.5, embryos are significantly delayed and appear as relatively pristine early egg-cylinder stage embryos
• however, no widespread active Trp53-positive apoptotic cells are detected at E7.5
|
• at E7.5, embryos are dramatically smaller than controls
(J:290315)
• embryos are much smaller than controls at E7.5
(J:279207)
|
cellular
N |
• embryos show no significant differences in 4HNE (4-hydroxynonenal) levels or localization relative to wild-type controls, suggesting no increase in lipid peroxidation or oxidative stress
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• embryos show a significantly higher ADP to ATP ratio, indicating mitochondrial dysfunction
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• at E7.5, TEM shows a marked alteration in mitochondrial morphology, with many large vesicle-like structures present within every mitochondrion
• however, the ratio of mitochondrial to nuclear genome content is similar to that in control embryos and only a slight increase in caspase-3 mediated apoptosis is noted in the embryonic portion
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• mitochondria exhibit far fewer cristae at E7.5
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• embryo sections show increased numbers of bright pH3 foci (pH3, a marker of dividing cells) relative to controls, suggesting that cells arrest in the G2/late G2 phase
• analysis of the phosphorylation status of Cdc25c (cell division cycle 25C) at serine 216 (S216) shows that embryos exhibit significantly more phospho-Cdc25c foci than littermates and stage-matched controls, indicating cell cycle arrest at the G2/M checkpoint
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• embryos show a significantly higher ADP to ATP ratio, indicating mitochondrial dysfunction
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• mitochondrial translation is impaired leading to a lack of ETC related proteins, as indicated by the absence of MT-CO2 protein (mitochondrially encoded cytochrome c oxidase II) in embryonic cells
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• absence of functional ETC components is likely responsible for the drastic reduction of ATP production
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homeostasis/metabolism
• embryos show a significantly higher ADP to ATP ratio, indicating mitochondrial dysfunction
|