HCM-linked ∆160E cardiac troponin T mutation causes unique progressive structural and molecular ventricular remodeling in transgenic mice

► A novel cTnT-linked hypertrophic cardiomyopathy mouse model was generated. ► Mutations in the unstructured linker domain of TNT1 cause sarcomeric disruption. ► Severe alterations in myocellular Ca2+ handling contribute to pathogenesis. ► Left ventricular remodeling was severe and dosage-dependent. ► These findings are consistent with both clinical and iPSC-based results.