Cardiac Troponin I C-Terminal Mutations (K178E and K179E) Cause Severe Heart Failure and Early Mortality in Transgenic Mice

Abstract

The C-terminal region of cardiac troponin I (cTnI164-210) plays an important role in cardiac muscle contraction. Most genetic cardiomyopathies in human are associated with the mutations in cTnI C-terminus. Among them, K178E mutation was reported to cause restrictive cardiomyopathy (RCM) in human. Deletion of K177 is related to hypertrophic cardiomyopathy (HCM). Since the amino acids numbered 173-181 bind to actin, which increases the inhibitory effect of TnI, we hypothesize that K177 and K178 are both critical for normal cardiac function.