TALEN-based generation of a cynomolgus monkey disease model for human   microcephaly

doi:10.1038/cr.2016.93

CORC > 北京大学 > 工学院

	TALEN-based generation of a cynomolgus monkey disease model for human microcephaly
	Ke, Qiong ; Li, Weiqiang ; Lai, Xingqiang ; Chen, Hong ; Huang, Lihua ; Kang, Zhuang ; Li, Kai ; Ren, Jie ; Lin, Xiaofeng ; Zheng, Haiqing ; Huang, Weijun ; Ma, Yunhan ; Xu, Dongdong ; Chen, Zheng ; Song, Xinming ; Lin, Xinyi ; Zhuang, Min ; Wang, Tao ; Zhuang, Fengfeng ; Xi, Jianzhong ; Mao, Frank Fuxiang ; Xia, Huimin ; Lahn, Bruce T. ; Zhou, Qi ; Yang, Shihua ; Xiang, Andy Peng
刊名	CELL RESEARCH
	2016
关键词	MCPH1 microcephaly TALEN gene mutant cynomolgus monkey PREMATURE CHROMOSOME CONDENSATION HUMAN BRAIN SIZE MOUSE MODEL MCPH1 GENE MUTATION PRIMATE RHESUS CELLS TELOMERASE CHECKPOINT
DOI	10.1038/cr.2016.93
英文摘要	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.; National Basic Research Program of China [2012CBA01302]; National Natural Science Foundation of China [81425016, 31301219, 81570593]; Fundamental Research Funds for the Central Universities [15ykjc01c]; PhD Programs Foundation of Ministry of Education of China [20130171120061]; Key Scientific and Technological Projects of Guangdong Province [2014B020226002, 2014B020228003, 2014B020225007, 2015B020228002, 2016B030229002]; Key Scientific and Technological Program of Guangzhou City [201400000003-3, 201508020262, 201300000089, 2010U1-E00551]; Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS); Pearl River S&T Nova Program of Guangzhou [2014J2200037]; SCI(E); PubMed; 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); ARTICLE; qzhou@ioz.ac.cn; yangsh@scau.edu.cn; xiangp@mail.sysu.edu.cn; 9; 1048-1061; 26
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/491442]
专题	工学院
推荐引用方式 GB/T 7714	Ke, Qiong,Li, Weiqiang,Lai, Xingqiang,et al. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly[J]. CELL RESEARCH,2016.
APA	Ke, Qiong.,Li, Weiqiang.,Lai, Xingqiang.,Chen, Hong.,Huang, Lihua.,...&Xiang, Andy Peng.(2016).TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.CELL RESEARCH.
MLA	Ke, Qiong,et al."TALEN-based generation of a cynomolgus monkey disease model for human microcephaly".CELL RESEARCH (2016).