A MOUSE MODEL OF FAMILIAL HYPERTROPHIC CARDIOMYOPATHY
Familial hypertrophic cardiomyopathy is a disease that is transmitted in an autosomal dominant fashion. The disease is associated with the myofibrillar disarray and leads to
cardiac hypertrophy. Many patients are asmptomatic. However, the disease may lead to shortness of breath, palpitations, heart failure or sudden death. Some individuals with the disease die during childhood whereas others survive to the 6th to 7th decades of their lives. In addition, the disease is associated with mutations in various proteins. These include missense mutations of the cardiac beta-myosin-heavy-chain (beta-MHC) gene, missense mutation in alpha-tropomyosin gene, mutation in the cardiac myosin binding protein-C gene splice acceptor site, and mutations in the cardiac myosin binding protein-C gene on chromosome 11. These observations suggest that familial hypertrophic cardiomyopathy may not be a single disease, rather it may represent a heterogeneous group of disorders.
In the May 3 issue of Science, Geisterfer-Lowrance et al describe the development of a mouse model of the disease. This was achieved by introduction of an Arg 403 to Gln mutation into the alpha cardiac myosin heavy chain (MHC). Homozygous mice died 7 days after birth and the heterozygous mice survived for 1 year. In these animals, evidence for cardiac dysfunction were apparent before the histophatologic changes of the cardiac muscle became evident. These changes were similar to the morphologic changes induced in the heart in the human familial hypertrophic cardiomyopathy. This model may be helpful in defining the natural history of the disorder.
Familial hypertrophic cardiomyopathy is a disease that is transmitted in an autosomal dominant fashion. The disease is associated with the myofibrillar disarray and leads to
cardiac hypertrophy. Many patients are asmptomatic. However, the disease may lead to shortness of breath, palpitations, heart failure or sudden death. Some individuals with the disease die during childhood whereas others survive to the 6th to 7th decades of their lives. In addition, the disease is associated with mutations in various proteins. These include missense mutations of the 
