Loss of DNA repair mechanisms in cardiac myocytes induce dilated cardiomyopathy.

ABSTRACT: Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1^-/D mice). Ckmm-Cre^+/- ;Ercc1^-/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre^+/- ;Ercc1^-/fl mice were structurally and functionally normal, but by 6-mont

SUBMITTER: Henpita C 

PROVIDER: S-EPMC10086531 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature