title: Generation of the SCN1A epilepsy mutation in hiPS cells using the TALEN technique.
abstract: Human induced pluripotent stem cells (iPSC) can be used to understand the pathological mechanisms of human disease. These cells are a promising source for cell-replacement therapy. However, such studies require genetically defined conditions. Such genetic manipulations can be performed using the novel Transcription Activator-Like Effector Nucleases (TALENs), which generate site-specific double-strand DNA breaks (DSBs) with high efficiency and precision. Combining the TALEN and iPSC methods, we developed two iPS cell lines by generating the point mutation A5768G in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 α subunit. The engineered iPSC maintained pluripotency and successfully differentiated into neurons with normal functional characteristics. The two cell lines differ exclusively at the epilepsy-susceptibility variant. The ability to robustly introduce disease-causing point mutations in normal hiPS cell lines can be used to generate a human cell model for studying epileptic mechanisms and for drug screening.
authors: 1] The School of Life Sciences, Anhui University, Hefei 230027 [2].
authors: Wanjuan
authors: W
authors: Chen
authors: 1] The School of Life Sciences, University of Science and Technology of China, Hefei 230027 [2].
authors: Jingxin
authors: J
authors: Liu
authors: The School of Life Sciences, University of Science and Technology of China, Hefei 230027.
authors: Longmei
authors: L
authors: Zhang
authors: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors: Huijuan
authors: H
authors: Xu
authors: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors: Xiaogang
authors: X
authors: Guo
authors: Xiang-Ya School of Medicine, Central South University.
authors: Sihao
authors: S
authors: Deng
authors: Xiang-Ya Boai Hospital, Changsha 410013, China.
authors: Lipeng
authors: L
authors: Liu
authors: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors: Daiguan
authors: D
authors: Yu
authors: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors: Yonglong
authors: Y
authors: Chen
authors: 1] Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China [2] Xiang-Ya School of Medicine, Central South University.
authors: Zhiyuan
authors: Z
authors: Li
mesh_terms: D002478:Cells, Cultured; D003851:Deoxyribonucleases / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D016297:Mutagenesis, Site-Directed / Q000379:methods*; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D015202:Protein Engineering / Q000379:methods
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D003851:Deoxyribonucleases