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Research Article Free access | 10.1172/JCI119063

Expression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy. Evidence for a dominant negative action.

H Watkins, C E Seidman, J G Seidman, H S Feng, and H L Sweeney

Department of Cardiovascular Medicine, University of Oxford, United Kingdom.

Find articles by Watkins, H. in: JCI | PubMed | Google Scholar

Department of Cardiovascular Medicine, University of Oxford, United Kingdom.

Find articles by Seidman, C. in: JCI | PubMed | Google Scholar

Department of Cardiovascular Medicine, University of Oxford, United Kingdom.

Find articles by Seidman, J. in: JCI | PubMed | Google Scholar

Department of Cardiovascular Medicine, University of Oxford, United Kingdom.

Find articles by Feng, H. in: JCI | PubMed | Google Scholar

Department of Cardiovascular Medicine, University of Oxford, United Kingdom.

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Published December 1, 1996 - More info

Published in Volume 98, Issue 11 on December 1, 1996
J Clin Invest. 1996;98(11):2456–2461. https://doi.org/10.1172/JCI119063.
© 1996 The American Society for Clinical Investigation
Published December 1, 1996 - Version history
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Abstract

Mutations in the beta-myosin heavy chain gene are believed to cause hypertrophic cardiomyopathy (HCM) by acting as dominant negative alleles. In contrast, a truncated cardiac troponin T (TnT) that causes HCM implies that altered stoichiometry of contractile proteins may also cause cardiac hypertrophy. Wild-type and HCM-mutant (truncated) TnT were studied in a novel quail myotube expression system. Unexpectedly, antibody staining demonstrated incorporation of both forms of human cardiac TnT into the sarcomeres of quail myotubes. Functional studies of wild type and mutant transfected myotubes of normal appearance revealed that calcium-activated force of contraction was normal upon incorporation of wild type TnT, but greatly diminished for the mutant TnT. These findings indicate that HCM-causing mutations in TnT and beta-myosin heavy chain share abnormalities in common, acting as dominant negative alleles that impair contractile performance. This diminished force output is the likely stimulus for hypertrophy in the human heart.

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  • Version 1 (December 1, 1996): No description

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