mortality/aging
• lethality occurs before E11.5
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growth/size/body
• significant delay and abnormal development is observed at E6.5, evidenced by abnormal mass of embryonic tissues relative to controls
• embryos at E7.5 and E8.5 show significant developmental retardation
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embryo
• elevated apoptosis is observed by E7.5 in mutant embryos, but at E6.5 there is little difference compared to controls
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• growth of the inner cell mass is impaired in cultured mutant blastocysts compared to wild-type starting at culture day 3 (equivalent to E6.5 in vivo)
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• no mesoderm differentiation is apparent at E7.5
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• developmental arrest is observed at E11.5
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• significant delay and abnormal development is observed at E6.5, evidenced by abnormal mass of embryonic tissues relative to controls
• embryos at E7.5 and E8.5 show significant developmental retardation
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• development of the neural plate is not evident at E8.5
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• development of the notochord is not evident at E8.5
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• amniotic cavity does not develop
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cellular
• elevated apoptosis is observed by E7.5 in mutant embryos, but at E6.5 there is little difference compared to controls
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• the proliferation index of cells in embryonic tissues is slightly reduced at E6.5 relative to controls and reduction is significant by E7.5
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• growth of the inner cell mass is impaired in cultured mutant blastocysts compared to wild-type starting at culture day 3 (equivalent to E6.5 in vivo)
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nervous system
• development of the neural plate is not evident at E8.5
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reproductive system
• litters are significantly smaller (5.1 pups/litter) than wild-type controls (10.3/litter)
• the number of double-positive transgenic offspring is greatly reduced, but some are viable; however, some of these animals were shown to have lost the RNAi cassette spontaneously
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