A mouse model of myosin binding protein C human familial hypertrophic cardiomyopathy

Qinglin Yang, Atsushi Sanbe, Hanna Osinska, Timothy E. Hewett, Raisa Klevitsky, Jeffrey Robbins

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

Familial hypertrophic cardiomyopathy can be caused by mutations in genes encoding sarcomeric proteins, including the cardiac isoform of myosin binding protein C (MyBP-C), and multiple mutations which cause truncated forms of the protein to be made are linked to the disease. We have created transgenic mice in which varying amounts of a mutated MyBP-C, lacking the myosin and titin binding domains, are expressed in the heart. The transgenically encoded, truncated protein is stable but is not incorporated efficiently into the sarcomere. The transgenic muscle fibers showed a leftward shift in the pCa2+-force curve and, importantly, their power output was reduced. Additionally, expression of the mutant protein leads to decreased levels of endogenous MyBP-C, resulting in a striking pattern of sarcomere disorganization and dysgenesis.

Original languageEnglish (US)
Pages (from-to)1292-1300
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number7
DOIs
StatePublished - Oct 1 1998

Keywords

  • Cardiomyopathy
  • Heart
  • Hypertrophy
  • Mouse
  • Transgenic

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'A mouse model of myosin binding protein C human familial hypertrophic cardiomyopathy'. Together they form a unique fingerprint.

  • Cite this