G.P.15.06 Inhibition of c-Jun N-terminal kinases signaling to prevent cardiomyopathy caused by mutation in LMNA gene

Abstract

Autosomal Emery-Dreifuss muscular dystrophy and related disorders with dilated cardiomyopathy and variable skeletal muscle involvement are caused by mutations in LMNA, which encodes ubiquitously expressed A-type nuclear lamins. How alterations in A-type lamins cause cardiomyopathy are poorly understood and the few hypotheses that have been raised have not been tested in physiologically relevant vertebrate animal models. We have previously demonstrated abnormal activation of both the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinases (JNK) branches of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of LMNA H222P ‘knock in’ mice, a model of autosomal Emery-Dreifuss muscular dystrophy.