A Mouse Model of Familial Hypertrophic Cardiomyopathy

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