Evaluation of a drug-target-molecule for demyelinating disorders using Dock7 knockdown mouse

在周围神经系统(PNS)的发育过程中，雪旺细胞(SCs)包裹轴突，形成一种称为髓鞘的多层结构，作为轴突周围的绝缘体。然而，到目前为止，促进髓鞘形成的特定治疗药物靶点仍然不清楚。在这项研究中，我们产生了新的表达DOCK7 shRNA的转基因小鼠，它降低了DOCK7的蛋白水平。我们描述了DOCK7的敲除在体内和体外都能特异性地促进髓鞘形成。据我们所知，这是一种可能的治疗靶分子的第一个报告，它可以在不减少轴突厚度的情况下促进髓鞘形成。

During development of the peripheral nervous system (PNS), Schwann cells (SCs) wrap axons to form a multilamellar structure called myelin, which functions as an insulator surrounding axons. In peripheral neuropathies such as Charcot-Marie-Tooth (CMT) disease, chronic demyelination and defective remyelination are repeated, causing more severe neuropathies. It is thus thought that development of a drug that promotes healthy myelination, with minimal side effects, may lead to useful therapeutic methods for these diseases. However, specific therapeutic drug targets that healthily promote myelination have hitherto remained unclear. In this study, we generated new transgenic mice expressing shRNA for Dock7, which knocked down Dock7 protein levels. We describe that knockdown of Dock7 specifically promotes myelination in vivo and in vitro. To the best of our knowledge, this is the first report of a possible therapeutic target molecule that promotes myelination without reduced axon thickness.