A truncated cardiac troponin T molecule in transgenic mice suggests multiple cellular mechanisms for familial hypertrophic cardiomyopathy.

摘要: Mutations in multiple cardiac sarcomeric proteins including myosin heavy chain (MyHC) and troponin T (cTnT) cause a dominant genetic heart disease, familial hypertrophic cardiomyopathy (FHC). Patients with mutations these two genes have quite distinct clinical characteristics. Those MyHC demonstrate more significant uniform hypertrophy variable frequency of sudden death. cTnT generally exhibit mild or no hypertrophy, but high death at an early age. To understand the basis for distinctions to study pathogenesis we created transgenic mice expressing truncated mouse allele analogous one found FHC patients. Mice low (< 5%) levels develop their hearts are significantly smaller (18-27%) than wild type. These animals also diastolic dysfunction milder systolic dysfunction. Animals that express higher transgene protein die within 24 h birth. Transgenic myocellular disarray reduced number myocytes size. studies suggest cellular mechanisms result human which is characterized by but, also, frequent