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https://hdl.handle.net/2440/51848
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Type: | Journal article |
Title: | Compensatory growth of healthy cardiac cells in the presence of diseased cells restores tissue homeostasis during heart development |
Author: | Drenckhahn, J. Schwarz, Q. Gray, S. Laskowski, A. Kiriazis, H. Ming, Z. Harvey, R. Du, X. Thorburn, D. Cox, T. |
Citation: | Developmental Cell, 2008; 15(4):521-533 |
Publisher: | Cell Press |
Issue Date: | 2008 |
ISSN: | 1534-5807 1878-1551 |
Statement of Responsibility: | Jörg-Detlef Drenckhahn, Quenten P. Schwarz, Stephen Gray, Adrienne Laskowski, Helen Kiriazis, Ziqiu Ming, Richard P. Harvey, Xiao-Jun Du, David R. Thorburn and Timothy C. Cox |
Abstract: | 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. |
Keywords: | Myocardium Heart Fetal Heart Myocytes, Cardiac Animals Mice, Knockout Mice beta-Galactosidase Lyases Green Fluorescent Proteins Organogenesis Homeostasis Pregnancy Heterozygote Mosaicism Genes, Reporter Transgenes Models, Cardiovascular Female Male X Chromosome Inactivation Embryo, Mammalian |
Rights: | Copyright © 2008 Elsevier B.V. All rights reserved. ScienceDirect® is a registered trademark of Elsevier B.V. |
DOI: | 10.1016/j.devcel.2008.09.005 |
Grant ID: | NHMRC |
Published version: | http://dx.doi.org/10.1016/j.devcel.2008.09.005 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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