Generation of a monkey with MECP2 mutations by TALEN-based gene targeting

作     者：Zhen Liu Xue Zhou Ying Zhu Zhi-Fang Chen Bin Yu Yan Wang Chen-Chen Zhang Yan-Hong Nie Xiao Sang Yi-Jun Cai Yue-Fang Zhang Chen Zhang Wen-Hao Zhou Qiang Sun Zilong Qiu 

作者机构：Institute of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Department of Neonatology Children’s Hospital of Fudan University State Key Laboratory of Biomembrane and Membrane Biotechnology School of Life Sciences PKU-IDG/McGovern Institute for Brain Research Peking University 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2014年第30卷第3期

页      面：381-386页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Basic Research Development Program of China (2011CBA00400 and 2011CB809102) the CAS Strategic Priority Research Program of China (XDB02050400) the National Key Technology R&D Program of China (2014BAI03B00) the CAS Hundreds of Talents Program of China (to Z.Q. and Q.S.) the National Science Foundation of China (91232712) 

主　　题：monkey TALEN MeCP2 Rett syndrome 

摘      要：Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey （Macaca fascicularis） carrying MECP2 mutations using transcription activator-like effector nucleases （TALENs）-mediated gene targeting. After injecting TALENs mRNA into monkey zygotes achieved by in vitro fertilization and embryo transplantation into surrogate monkeys, we obtained one male newborn monkey with an MECP2 deletion caused by frame- shifting mutation in various tissues. The monkey carrying the MECP2 mutation failed to survive after birth, due to either the toxicity of TALENs or the critical requirement of MECP2 for neural development. The level of MeCP2 protein was essentially depleted in the monkey＇s brain. This study demonstrates the feasibility of introducing genetic mutations in non-human primates by site-specific gene-editing methods.