Expression of a truncated MyBP-C lacking myosin and titin binding domains in transgenic mice led to sarcomere disorganization, increased Ca2+ sensitivity, and decreased maximum power output.
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.
Yang et al. (Thu,) conducted a other in Familial hypertrophic cardiomyopathy (FHC). Transgenic expression of mutated MyBP-C (MyBP-C.mut1) vs. Nontransgenic littermates and wild-type MyBP-C transgenic mice was evaluated on Sarcomere organization and cardiac fiber mechanics (Ca2+ sensitivity and power output). Expression of a truncated MyBP-C lacking myosin and titin binding domains in transgenic mice led to sarcomere disorganization, increased Ca2+ sensitivity, and decreased maximum power output.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: