Abstract 18980: N-terminal Region of Cardiac Myosin Binding Protein-C Regulates Sarcomeric and Cardiac Function

Rationale: Cardiac myosin binding protein-C (cMyBP-C) is a trans-filament protein that can bind both the thick and thin filaments and regulate contraction. Previously we showed that decreased cMyBP-C phosphorylation is directly associated with catalytic cleavage of the first 271 residues of the N-terminal (N’) and, as a consequence, contractile dysfunction. This region has been shown to be largely responsible for the actin-myosin interacting properties of cMyBP-C and was postulated to regulate sarcomere sliding velocity. However, it is unknown whether it is necessary to regulate contractile function. Hypothesis: N’-region of cMyBP-C is essential for sarcomeric and cardiac function. Methods and Results: To determine the necessity of N’-region, we generated transgenic mice (C57BL/6) expressing a truncated 110kDa cMyBP-C lacking the first 271 amino acids (Tg110). Compared to non-transgenic litter-mates (NTG), Tg110 mice demonstrate high replacement levels of native cMyBP-C (>95%). Truncated cMyBP-C localized...