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). Here, ERCC1 is linked to cardiomyopathy.