W K Jones, I L Grupp, T Doetschman, G Grupp, H Osinska, T E Hewett, G Boivin, J Gulick, W A Ng, J Robbins
J Clin Invest.
1996;
98(8):1906–1917
doi:10.1172/JCI118992
This article Copyright © 1996, The American Society for Clinical Investigation
Abstract
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T
he 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.
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