title: TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.
abstract: Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size.
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510623, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.|Department of Biology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Key Laboratory of Reproductive Medicine, Guangzhou 510080, China.
authors: Qiong
authors: Q
authors: Ke
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510623, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Key Laboratory of Reproductive Medicine, Guangzhou 510080, China.|Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Weiqiang
authors: W
authors: Li
authors: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Xingqiang
authors: X
authors: Lai
authors: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Hong
authors: H
authors: Chen
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510623, China.
authors: Lihua
authors: L
authors: Huang
authors: Department of Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510632, China.
authors: Zhuang
authors: Z
authors: Kang
authors: Department of Ultrasound, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510632, China.
authors: Kai
authors: K
authors: Li
authors: Department of Ultrasound, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510632, China.
authors: Jie
authors: J
authors: Ren
authors: Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors: Xiaofeng
authors: X
authors: Lin
authors: Department of Rehabilitation Medicine Science, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510632, China.
authors: Haiqing
authors: H
authors: Zheng
authors: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Weijun
authors: W
authors: Huang
authors: College of Veterinary Medicine, Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, South China Agricultural University, Guangzhou 510642, China.
authors: Yunhan
authors: Y
authors: Ma
authors: College of Veterinary Medicine, Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, South China Agricultural University, Guangzhou 510642, China.
authors: Dongdong
authors: D
authors: Xu
authors: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors: Zheng
authors: Z
authors: Chen
authors: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors: Xinming
authors: X
authors: Song
authors: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors: Xinyi
authors: X
authors: Lin
authors: School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors: Min
authors: M
authors: Zhuang
authors: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.|Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Tao
authors: T
authors: Wang
authors: Beijing ViewSolid Biotechnology, Beijing 100034, China.
authors: Fengfeng
authors: F
authors: Zhuang
authors: Department of Biomedical Engineering, College of Engineering, Peking University, Yannan Yuan 60, Beijing 100871, China.
authors: Jianzhong
authors: J
authors: Xi
authors: State Key Laboratory of Ophthalmology, Zhong Shan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Frank Fuxiang
authors: FF
authors: Mao
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510623, China.
authors: Huimin
authors: H
authors: Xia
authors: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors: Bruce T
authors: BT
authors: Lahn
authors: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Qi
authors: Q
authors: Zhou
authors: College of Veterinary Medicine, Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, South China Agricultural University, Guangzhou 510642, China.
authors: Shihua
authors: S
authors: Yang
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510623, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Key Laboratory of Reproductive Medicine, Guangzhou 510080, China.|Department of Biochemistry, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510080, China.
authors: Andy Peng
authors: AP
authors: Xiang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006801:Humans; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008831:Microcephaly / Q000473:pathology*; D009154:Mutation; D010641:Phenotype; D000069896:Transcription Activator-Like Effector Nucleases / Q000378:metabolism*
chemical_list: D000069896:Transcription Activator-Like Effector Nucleases