Analysis Tools
mortality/aging
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• homozygous embryos die at ~E9.5; no viable homozygotes are born
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growth/size/body
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• all embryos exhibit severe growth retardation at E9.5
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• average size of E9.5 embryos is less than half of wild-type controls
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homeostasis/metabolism
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• E9.5 embryos show an ~80% reduction of the fully assembled mitochondrial ATP synthase complex (F1Fo, CV) along with a 3.5-4-fold accumulation of F1-complexes, resulting in a 20-fold increase in the F1/F1Fo ratio
• impaired ATP synthase biogenesis is stalled at an early stage, following the formation of F1 oligomer
• however, content of respiratory chain (RC) enzymes is near-normal at E9.5
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embryo
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• body curvature is often still in a lordotic-like curvature at E9.5
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• all embryos exhibit severe growth retardation at E9.5
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• average size of E9.5 embryos is less than half of wild-type controls
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• E9.5 embryos exhibit an open anterior neuropore, consistent with a 1-day developmental delay
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• E9.5 embryos contain less than 15 somites compared to 25 somites seen in controls
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cardiovascular system
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• E9.5 hearts are significantly smaller but show normal looping and differentiation into proper compartments, consistent with a 1-day developmental delay
• colonization of cardiac cushions by mesenchymal cells is significantly reduced, resembling the situation at E8.5 with only a few cells entering the cardiac jelly
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small heart
(
J:238642
)
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• hearts are significantly smaller at E9.5
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cellular
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• ~80% of heart mitochondria show fewer cristae with altered morphology at E9.5
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• in heart mitochondria, the normal arrangement of trabecular cristae is often replaced by concentric or irregular cristae structures
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• ~80% of heart mitochondria show atypical shapes at E9.5
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• impaired mitochondrial ATP production
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• homogenates of E9.5 embryos show significantly reduced rates of ADP-stimulated (State 3) oxidation of respiratory chain (RC) substrates (pyruvate+glutamate+malate+succinate) normalized to RC content
• specific activity of oligomycin-sensitive oxidation of these substrates (State 3-State 4) is reduced by 68-71%
• 2-fold decrease in the respiratory control ratio (State 3/State 4)
• 2-fold decrease in the ATP/ADP ratio
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• upregulation in the content of mitochondrial Mn-dependent superoxide dismutase (SOD2), indicating higher levels of oxidative stress
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nervous system
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• E9.5 embryos exhibit an open anterior neuropore, consistent with a 1-day developmental delay
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