Generation of iPS cells derived form an Rett syndrome model mouse and drug screening for Rett syndrome using MeCP2 deficient iPS cells

Rett综合征（RTT）是一种与甲基CpG？结合蛋白2（MeCP 2）基因。MeCP 2缺陷小鼠重现了RTT患者中观察到的神经变性。诱导性多能干细胞（induced pluripotetn stem，iPS）的产生是理解遗传学和复杂疾病发病机制的关键步骤。在这里，我们通过慢病毒递送共表达四种因子（Oct 3/4，Sox 2，Klf 4和c-Myc）从MeCP 2缺陷小鼠产生RTT模型小鼠iPS细胞系，并将其分化为神经元细胞用于进一步分析。RTT模型iPS细胞的特征在于多能标记物的表达和它们通过在体外形成胚状体分化成所有三个胚层的能力。此外，SDIA诱导的WT和RTT模型iPS细胞系的集落产生了具有神经元样形态的细胞，其表达神经元标记物微管相关蛋白2（MAP 2），一种神经元特异性微管蛋白β III型。我们的RTT模型iPS细胞系为基础神经科学研究和治疗应用提供了强大的工具。

Rett syndrome (RTT) is a neurodevelopmetal disorder associated with mutations in the methyl-CpG?binding protein 2 (MeCP2) gene. MeCP2-deficient mice recapitulate the neurological degeneration observed in RTT patients. The generation of diseased induced pluripotetn stem (iPS) cell is a critical step in understanding the pathogenesis of genetics and complex diseases. Here, we generated RTT-model mouse iPS cell lines from MeCP2-deficient mouse by co-expressing four factors (Oct3/4, Sox2, Klf4, and c-Myc) throughlentiviraldeliveryandsubsequentlydifferentiatedthemintoneuronalcellsfor further analyses. RTT-model iPS cells were characterized for the expression of pluripotent markers and for their ability to differentiate into all three germ layers by forming embryoid bodies in vitro. In addition, SDIA-induced colonies from both WT and RTT-model iPS cell lines generated cells possessing neuronal-like morphologies that expressed neuronal markers microtubule-associated protein 2 (MAP2) an neuron-specific tubulin beta type III. Our RTT-model iPS cell lines provide a powerful tool for both basic neuroscience research and therapeutic applications.