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J Clin Invest. 1996 Oct 15;98(8):1906-17.

Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart.

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1
Division of Molecular Cardiovascular Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.

Abstract

The alpha-myosin heavy chain (alpha-MyHC) is the major contractile protein expressed in the myocardium of adult mice. We have produced mice carrying a null mutation of alpha-MyHC by homologous recombination in murine ES cells. Homozygous null animals die between 11 and 12 d in utero of gross heart defects, while alpha-MyHC+/- heterozygotes survive and appear externally normal. The presence of a single functional alpha-MyHC+ allele in heterozygous animals results in reduced levels of the transcript and protein as well as fibrosis and alterations in sarcomeric structure. Examination of heart function using a working heart preparation revealed severe impairment of both contractility and relaxation in a subset of the alpha-MyHC+/- animals. Thus, two alpha-MyHC+ alleles are necessary for normal cardiac development, and hemizygosity for the normal allele can result in altered cardiac function.

PMID:
8878443
PMCID:
PMC507631
DOI:
10.1172/JCI118992
[Indexed for MEDLINE]
Free PMC Article
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