A murine model for hypertrophic cardiomyopathy.

A leading cause of sudden death among young athletes is the autosomal dominant genetic heart disease, familial hypertrophic cardiomyopathy (FHC). Mutations in several contractile proteins, including cardiac myosin heavy chains, have been described in families with FHC, leading to the hypothesis that FHC is a disease of the sarcomere (17). To create an animal model for this disease, five lines of transgenic mice have been produced that express a mutant myosin heavy chain in their hearts. The hearts of these mice exhibit the histopathological features seen in patients and demonstrate enlarged left ventricles. Our analysis suggests that the mutant protein acts as a dominant negative, since it constitutes only 5-10% of the total myosin in the heart. In addition, while the transgene is expressed in all chambers of the heart, only the left ventricle demonstrates pathology and enlargement, suggesting that several prominent features of the disease represent secondary responses influenced by other factors, such as hemodynamics.