Transgenic D94A mice with a novel MYL2 mutation developed hypocontractile myosin motors and structural perturbations leading to left ventricular chamber dilation and decreased ejection fraction.
The MYL2 D94A mutation causes hypocontractile myosin motors and structural perturbations leading to dilated cardiomyopathy, highlighting MYL2 as a potential therapeutic target.
Significance Dilated cardiomyopathy (DCM) is a progressive heart disease with no current cure, often culminating in heart transplantation. Transgenic D94A (aspartic acid-to-alanine) mice carrying a novel DCM-causative mutation in the MYL2 gene, encoding the cardiac myosin regulatory light chain, were created and investigated by echocardiography and invasive hemodynamic and molecular structural and functional assessments. Our data show that hypocontractile myosin motors and structural perturbations at the level of sarcomeres trigger aberrant functional remodeling in D94A hearts and the development of DCM, which closely follows the clinical phenotype. Left ventricular chamber dilation and decreased ejection fraction, observed in D94A hearts, were indicative of systolic dysfunction, a hallmark of DCM. Our study suggests that MYL2 may be considered a therapeutic target for dilated cardiomyopathy.
Yuan et al. (Tue,) conducted a other in Dilated cardiomyopathy. D94A mutation in MYL2 gene was evaluated on Left ventricular chamber dilation and decreased ejection fraction. Transgenic D94A mice with a novel MYL2 mutation developed hypocontractile myosin motors and structural perturbations leading to left ventricular chamber dilation and decreased ejection fraction.