BioProject

We have recently shown a remarkable regenerative capacity of the prenatal heart using a genetic model of mosaic mitochondrial dysfunction in mice. More...

We have recently shown a remarkable regenerative capacity of the prenatal heart using a genetic model of mosaic mitochondrial dysfunction in mice. This model is based on inactivation of the X-linked gene encoding holocytochrome c synthase (Hccs) specifically in the developing heart. Loss of HCCS activity results in respiratory chain dysfunction, disturbed cardiomyocyte differentiation and reduced cell cycle activity. The Hccs gene is subjected to X chromosome inactivation, such that in females heterozygous for the heart conditional Hccs knockout approximately 50% of cardiac cells keep the defective X chromosome active and develop mitochondrial dysfunction while the other 50% remain healthy. During heart development, however, the contribution of HCCS deficient cells to the cardiac tissue decreases from 50% at midgestation to 10% at birth. This regeneration of the prenatal heart is mediated by increased proliferation of the healthy cardiac cell population, which compensate for the defective cells and allow the formation of a fully functional heart at birth. Here we performed microarray expression ananlyses on 13.5 dpc control and heterozygous Hccs knockout hearts to identify molecular mechanisms that drive embryonic heart regeneration. Overall design: 13.5 dpc hearts of heterozygous heart conditional Hccs knockout and littermate control female embryos were dissected, RNA was isolated and hybridized to Affymetrix arrays. At this developmental stage the most dramatic changes in tissue composition occur in the knockouts, as hyperproliferation of healthy cardiomyocytes is readily detectable while a substantial contribution of HCCS deficient cells is still present. 5 biological replicates per genotyp each containing 4-5 pooled hearts were analyzed. Less...