Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.
Glia. 2011 Jul;59(7):1022-32. doi: 10.1002/glia.21173. Epub 2011 Apr 12.
The transcription factor Sox10 functions during multiple consecutive stages of Schwann-cell development in the peripheral nervous system (PNS). Although Sox10 continues to be expressed in mature Schwann cells of the adult peripheral nerve, it is currently unclear whether it is still functional. Here, we used a genetic strategy to selectively delete Sox10 in glia of adult mice in a tamoxifen-dependent manner. The tamoxifen-treated mice developed a severe peripheral neuropathy that was associated with dramatic alterations in peripheral nerve structure and function. Demyelination and axonal degeneration were as much evident as signs of neuroinflammation. Compound action potentials exhibited pathophysiological alterations. Sox10-deleted Schwann cells persisted in the peripheral nerve, but did not exhibit a mature, myelinating phenotype arguing that Sox10 is rather required for differentiation and maintenance of the differentiated state than for survival. Our report is the first evidence that Sox10 is still essentially required for Schwann-cell function in the adult PNS and establishes a useful model in which to study human peripheral neuropathies.
转录因子 Sox10 在周围神经系统 (PNS) 中的施万细胞发育的多个连续阶段中发挥作用。尽管 Sox10 在成年周围神经的成熟施万细胞中持续表达，但目前尚不清楚它是否仍然具有功能。在这里，我们使用遗传策略以他莫昔芬依赖性的方式在成年小鼠的神经胶质细胞中选择性地删除 Sox10。经他莫昔芬处理的小鼠发生了严重的周围神经病，其与周围神经结构和功能的明显改变相关。脱髓鞘和轴突变性与神经炎症的迹象一样明显。复合动作电位表现出病理生理改变。Sox10 缺失的施万细胞在周围神经中持续存在，但未表现出成熟的髓鞘形成表型，这表明 Sox10 对于分化和维持分化状态而不是生存更为必需。我们的报告首次证明 Sox10 在成年 PNS 中的施万细胞功能中仍然是必需的，并建立了一个有用的模型，可用于研究人类周围神经病变。
