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-Null 胚胎干细胞的神经发育：研究 Rett 综合征的系统

• 批准号: 20790756
• 负责人: OKABE Yasunori
• 金额: $ 2.75万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790756/
• 关键词: 再生医学; 遺伝子疾患; 脳神経疾患; 胚性幹細胞

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.

甲基-CPG结合蛋白2（MECP2）基因的突变导致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。我们已经开发了一种新型的RTT模型系统，该系统能够检查MECP2在整个细胞水平上的作用。我们研究MECP2 null ES细胞在体外神经元分化过程中的研究表明，MECP2对于维持或生长未分化的细胞或神经发生的发展不是必不可少的。但是，MECP2是ES细胞衍生的神经元以及正常电压门控的Na^+电流和IAS的成熟所必需的。此外，我们表明MECP2缺乏导致神经胶质发生急剧增加。我们的新型实验系统使我们能够解决与MECP2相关的发育生物学和有关RTT发病机理的争议的重要问题，并可能有助于未来RTT治疗策略的发展。

项目成果

Thiamylal antagonizes the inhibitory effects of dorsal column stimulation on dorsal horn activities in humans

硫淀粉醛拮抗背柱刺激对人体背角活动的抑制作用

• 发表时间: 2009
• 期刊: Neuroscience Research 64
• 作者: Eiichiro Tanaka;Toshiyuki Tobita;Yoshinaka Murai;Yasunori Okabe;Aya Yamada;Tatsuhiko Kano;Hideho Higashi;Koki Shimoji
• 通讯作者: Koki Shimoji