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Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that target proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR) and the muscle-specific kinase. Because downstream of kinase 7 (Dok-7) is essential for the full activation of muscle-specific kinase and consequently for dense clustering of AChRs, we hypothesized that reduced levels of Dok-7 increase the susceptibility to passive transfer MG. To test this hypothesis, Dok-7 expression was reduced by transfecting shRNA-coding plasmids into the tibialis anterior muscle of adult rats by in vivo electroporation. Subclinical MG was subsequently induced with a low dose of anti-AChR monoclonal antibody 35. Neuromuscular transmission was significantly impaired in Dok-7-siRNA-electroporated legs compared with the contralateral control legs, which correlated with a reduction of AChR protein levels at the neuromuscular junction (approximately 25%) in Dok-7-siRNA-electroporated muscles, compared with contralateral control muscles. These results suggest that a reduced expression of Dok-7 may play a role in the susceptibility to passive transfer MG, by rendering AChR clusters less resistant to the autoantibody attack.

Original publication




Journal article


Am J Pathol

Publication Date





2559 - 2568


Animals, Autoantibodies, Disease Models, Animal, Disease Susceptibility, Down-Regulation, Female, Gene Silencing, Genes, Reporter, HEK293 Cells, Humans, Muscle Proteins, Muscle, Skeletal, Myasthenia Gravis, Autoimmune, Experimental, Neuromuscular Junction, Rats, Rats, Inbred Lew, Receptor Protein-Tyrosine Kinases, Receptors, Cholinergic, Synaptic Transmission