A Mouse Model of Familial Hypertrophic Cardiomyopathy

A mouse model of familial hypertrophic cardiomyopathy (FHC) was generated by the introduction of an Arg403 → Gln mutation into the α cardiac myosin heavy chain (MHC) gene. Homozygous αMHC403/403 mice died 7 days after birth, and sedentary heterozygous αMHC403/+ mice survived for 1 year. Cardiac histopathology and dysfunction in the αMHC403/+ mice resembled human FHC. Cardiac dysfunction preceded histopathologic changes, and myocyte disarray, hypertrophy, and fibrosis increased with age. Young male αMHC403/+ mice showed more evidence of disease than did their female counterparts. Preliminary results suggested that exercise capacity may have been compromised in the αMHC403/+ mice. This mouse model may help to define the natural history of FHC.