mortality/aging
• embryos die as a result of cardiomyopathy after E14.5
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cellular
• cardiomyocytes show an increase in acetylated tubulin staining suggesting an increase in microtubule stability
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• at E13.5, gamma-tubulin staining showed abnormal formation of multiple centrosomes in mitotic cardiac myocytes
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• cardiomyocytes exhibit impaired karyokinesis and multiple centrosomes
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• mitotic cardiomyocytes lack a bipolar spindle at metaphase; instead, spindles are deformed with irregular aggregated chromosomes
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cardiovascular system
• at E13.5, 91% of cardiomyocytes exhibit an abnormal shape
• 9% of cardiomyocytes are binucleated
• nuclei are irregular and significantly larger, sometimes exhibiting a multilobed appearance
• mitotic cardiomyocytes lack a bipolar spindle; instead, spindles are deformed with irregular aggregated chromosomes
• however, sarcomere formation is normal in E13.5 cardiac myocytes
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• at E13.5, hearts exhibit a marked reduction in cardiomyocytes
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• embryonic heart is severely hypoplastic; however, numbers of cardiac myocytes are sufficient to support life to E14.5
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muscle