Compensatory Growth of Healthy Cardiac Cells in the Presence of Diseased Cells Restores Tissue Homeostasis during Heart Development
Joerg-Detief Drenckhahn, Quenten P Schwarz, Stephen Gray, Adrienne Laskowski, Helen Kiriazis, Ziqiu Mings, Richard P Harvey, Xiao-Jun Du, David R Thorburn, Timothy C Cox
DEVELOPMENTAL CELL | CELL PRESS | Published : 2008
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 progres..View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
Initial stages of this work were supported by an Australian National Health and Medical Research Council (NHMRC) Project Grant (000125). NHMRC R. Douglas Wright Award, and Keith Sheridan Associateship (University of Adelaide Medical Endowment Fund) to T.C.C. J.D.D. was supported by a research fellowship and a project grant from the German Research Council (Deutsche Forschungsgemeinschaft, DFG). D.R.T. was supported by grants and a Senior Research Fellowship from the NHMRC and by the Muscular Dystrophy Association. X.J.D. is a fellow of the NHMRC. We thank Liza Cox and Patrick Tam (Childrens Medical Research Institute. Westmead, NSW, Australia) for the D4X reporter mice, and Nigel Wreford (Department of Anatomy and Developmental Biology, Monash University, Melbourne. VIC, Australia) for assistance with the stereology analyses. The authors declare they have no competing financial interests.