LMO7-NULL MICE EXHIBIT PHENOTYPES CONSISTENT WITH EMERY-DREIFUSS MUSCULAR DYSTROPHY

Introduction: Mutations in the inner nuclear envelope protein emerin cause Emery-Dreifuss muscular dystrophy (EDMD), which is characterized by progressive skeletal muscle wasting, cardiac conduction defects, and tendon contractures. We previously showed that emerin binds directly to the transcription regulator Lmo7 and attenuates its activity to regulate the proper temporal expression of important myogenic differentiation genes. Methods: The skeletal muscle and cardiac phenotypes were analyzed in a newly generated Lmo7-null mouse using histological analysis, echocardiography, and various neuromuscular tests to determine if Lmo7 was important for skeletal muscle and cardiac function. Results: Lmo7-null mice had growth retardation, decreased fiber size, and impaired skeletal muscle and cardiac function. Lmo7-null mice also had lower levels of phosphorylated retinoblastoma (Rb), extracellular signal-regulated kinase, and c-Jun N-terminal kinase, which is consistent with altered Rb and mitogen-activated protein kinase signaling. Conclusions: These findings demonstrate that loss of Lmo7 in mice causes myopathic phenotypes similar to those seen in other EDMD mouse models. Muscle Nerve 51: 222-228, 2015