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. © 2008 Elsevier Inc. All rights reserved.
Drenckhahn, J. D., Schwarz, Q. P., Gray, S., Laskowski, A., Kiriazis, H., Ming, Z., … Cox, T. C. (2008). Compensatory Growth of Healthy Cardiac Cells in the Presence of Diseased Cells Restores Tissue Homeostasis during Heart Development. Developmental Cell, 15(4), 521–533. https://doi.org/10.1016/j.devcel.2008.09.005