Emery-Dreifuss muscular dystrophy (EDMD) is characterized mainly by defects in heart and muscle function and is caused by mutations in one of two genes LMNA and EMD. But how mutations in LMNA lead to heart disease had not been determined.
In a study appearing online on April 19 in advance of publication in the May print issue of the Journal of Clinical Investigation, Howard Worman and colleagues from Columbia University, New York, used a mouse model of EDMD to define the signaling proteins activated in cells expressing mutated Lmna.
Heart muscle cells isolated from these mice expressed high levels of signaling proteins known as MAPKs and high levels of MAPK activity. Importantly, overexpression of the protein made by the mutated Lmna gene in cultured heart muscle cells also induced the activation of MAPKs.
This study indicates that activation of MAPKs is likely to contribute substantially to the defects in heart function in individuals with EDMD caused by mutations in LMNA, leading the authors to suggest that drugs inhibiting these signaling proteins might be of benefit for individuals with EDMD.