[HTML][HTML] Silencing of Dok-7 in adult rat muscle increases susceptibility to passive transfer myasthenia gravis
AM Gomez, JAA Stevens, M Mané-Damas… - The American Journal of …, 2016 - Elsevier
AM Gomez, JAA Stevens, M Mané-Damas, P Molenaar, H Duimel, F Verheyen, J Cossins…
The American Journal of Pathology, 2016•ElsevierMyasthenia 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 …
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 …
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.
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