Compensatory growth of healthy cardiac cells in the presence of diseased cells restores tissue homeostasis during heart development

Jorg-Detlef Christian Drenckhahn, Quenten P Schwarz, Stephen Peter Gray, Adrienne Laskowski, Helen Kiriazis, Z Ming, Richard P Harvey, Xiao-Jun Du, David R Thorburn, Timothy Chilton Cox

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118 Citations (Scopus)


Energy generation by mitochondrial respiration is an absolute requirement for cardiac function. Here, we used a heart-specific conditional knockout approach to inactivate the X-linked gene encoding Holocytochrome c synthase (Hccs), an enzyme responsible for activation of respiratory cytochromes c and c1. Heterozygous knockout female mice were thus mosaic for Hccs function due to random X chromosome inactivation. In contrast to midgestational lethality of Hccs knockout males, heterozygous females appeared normal after birth. Analyses of heterozygous embryos revealed the expected 50:50 ratio of Hccs deficient to normal cardiac cells at midgestation; however, diseased tissue contributed progressively less over time and by birth represented only 10 of cardiac tissue volume. This change is accounted for by increased proliferation of remaining healthy cardiac cells resulting in a fully functional heart. These data reveal an impressive regenerative capacity of the fetal heart that can compensate for an effective loss of 50 of cardiac tissue.
Original languageEnglish
Pages (from-to)521 - 533
Number of pages13
JournalDevelopmental Cell
Issue number4
Publication statusPublished - 2008

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