A Mouse Model of Familial Hypertrophic Cardiomyopathy

TLDR

The study aims to use a mouse model to delineate the natural history of familial hypertrophic cardiomyopathy. The authors engineered a FHC mouse by introducing an Arg403Gln mutation into the α‑cardiac myosin heavy chain gene. Heterozygous mice survived a year but developed progressive cardiac dysfunction and histopathologic changes resembling human FHC, with males showing more severe disease and reduced exercise capacity, while homozygotes died within a week.

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.