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

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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.