Neural Development of Methyl-CpG-Binding Protein 2-Null Embryonic Stem Cells : A System for Studing Rett Syndrome

甲基CpG结合蛋白2(MeCP2)基因的突变会导致Rett综合征(RTT)，这是一种神经发育障碍，是女性智力低下的主要原因。我们开发了一种新的RTT模型系统，能够在细胞水平上研究MeCP2在整个发育过程中的作用。我们在体外神经元分化过程中对MeCP2缺失ES细胞的研究表明，MeCP2对未分化细胞的维持或生长或神经发生的进展不是必需的。然而，MeCP2是ES细胞来源的神经元成熟所必需的，也是正常电压门控钠电流和IAS所必需的。此外，我们还发现MeCP2缺乏导致神经胶质生成显著增加。我们新颖的实验系统使我们能够解决MeCP2相关发育生物学中的重要问题和关于RTT发病机制的争议，并可能有助于未来RTT治疗策略的发展。

Mutations in methyl-CpG-binding protein 2 (MeCP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder that is the leading cause of mental retardation in females. We have developed a novel RTT model system that enables examination of the role of MeCP2 throughout development at the cellular level. Our study examining MeCP2 null ES cells during in vitro neuronal differentiation showed that MeCP2 is not essential for the maintenance or growth of undifferentiated cells or for the progression of neurogenesis. However, MeCP2 is required for the maturation of ES cell-derived neurons and for normal voltage-gated Na^+ currents and IAs. Furthermore, we showed that MeCP2 deficiency led to dramatically increased gliogenesis. Our novel experimental system has permitted us to address both important issues in MeCP2-related developmental biology and controversies regarding the pathogenesis of RTT, and may aid in the development of therapeutic strategies for RTT in the future.