Mice Expressing Mutant Myosin Heavy Chains Are a Model for Familial Hypertrophic Cardiomyopathy

摘要: Familial hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by ventricular hypertrophy, myocellular disarray, arrhythmias, and sudden death. Mutations in several contractile proteins, including cardiac myosin heavy chains, have been described families with this disease, leading to the hypothesis that HCM a of sarcomere. A mutation chain (Myh) predicted interfere strongly myosin’s binding actin was designed used create animal model for HCM. Five independent lines transgenic mice were produced cardiac-specific expression mutant Myh. Although Myh represents small proportion (1–12%) heart’s myosin, exhibit histopathology seen patients. Histopathology absent from atria primarily restricted left ventricle. The line exhibiting highest level demonstrates hypertrophy 12 weeks age, but further course affected sex animal. Hypertrophy increases age female animals while hearts male show severe dilation 8 months absence increased mass. low levels transgene protein presence phenotypic features suggest acts as negative. In addition, distinct phenotypes developed aging or extragenic factors influence development phenotype.