Analysis Tools
mortality/aging
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• although homozygous embryos appeared grossly normal from E9.5 to E10.5, nearly 50% died and began to undergo resorption at E11.5
• most embryos died by E12.5, with no live embryos recovered at E13.5
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cardiovascular system
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• cardinal veins were enlarged at E10.5, as shown by PECAM staining
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• trabeculae were smaller and thinner by E11.5
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• at E10.5, cardiomyocytes showed a significant increase in thin filament length relative to those in wild-type controls
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• hearts appeared more rounded in shape at E10.5
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small heart
(
J:256653
)
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• hearts were slightly smaller than normal, starting from E10.5
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• heart left ventricles were markedly smaller in size at E11.5
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• right ventricular wall was thinner by E11.5
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• % of proliferative (pHH3-positive) cardiomyocytes was significantly decreased only at E11.5, but not earlier, suggesting that proliferation defects were likely to be a secondary to cardiac dysfunction
• cleaved Caspase-3 puncta were barely detected in cardiomyocytes from E9.5 to E11.5
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muscle
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• trabeculae were smaller and thinner by E11.5
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• % of proliferative (pHH3-positive) cardiomyocytes was significantly decreased only at E11.5, but not earlier, suggesting that proliferation defects were likely to be a secondary to cardiac dysfunction
• cleaved Caspase-3 puncta were barely detected in cardiomyocytes from E9.5 to E11.5
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• at E11.5, cardiomyocyte sarcomeres appeared poorly organized; expression of the actin nucleator Lmod2 was up-regulated by 2- to 3-fold, and a portion of the pointed end capping protein Tmod1 was mislocalized in the cytoplasm, consistent with defects in thin filament assembly
• at E9.5, E10.5 and E11.5, cardiomyocyte sarcomeres exhibited abnormal actin bundles (AABs) which were continuous throughout the length of the sarcomere and associated with alpha-actinin; AABs included Z-line components but lacked troponin-tropomyosin complexes, and neither myomesin nor myosin heavy chain were detected, indicating that AABs were non-contractile
• at E10.5, thin filament length was significantly increased in cardiomyocyte sarcomeres
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• at E11.5, cardiomyocyte Z lines were narrower and had a checkerboard appearance
• atypical structures, designated abnormal actin bundles (AABs), that interconnected Z lines and were cross-linked by alpha-actinin were seen as early as E9.5; AABs included Z-line components (alpha-actinin, cypher and, in rare cases, titin) but lacked thin filament (Tpm1, cTnT) or thick filament components (myosin heavy chain, myomesin), indicating that AABs are aberrant Z-line structures unlikely to contract independently
• M lines were relatively unchanged
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cellular
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• % of proliferative (pHH3-positive) cardiomyocytes was significantly decreased only at E11.5, but not earlier, suggesting that proliferation defects were likely to be a secondary to cardiac dysfunction
• cleaved Caspase-3 puncta were barely detected in cardiomyocytes from E9.5 to E11.5
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