title: TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys.
abstract: Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in nonhuman primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett syndrome (RTT) gene, methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. Microinjection of MECP2-targeting TALEN plasmids into rhesus and cynomolgus zygotes leads to effective gene editing of MECP2 with no detected off-target mutagenesis. Male rhesus (2) and cynomolgous (1) fetuses carrying MECP2 mutations in various tissues including testes were miscarried during midgestation, consistent with RTT-linked male embryonic lethality in humans. One live delivery of a female cynomolgus monkey occurred after 162 days of gestation, with abundant MECP2 mutations in peripheral tissues. We conclude that TALEN-mediated mutagenesis can be an effective tool for genetic modeling of human disease in nonhuman primates.
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Hailiang
authors: H
authors: Liu
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
authors: Yongchang
authors: Y
authors: Chen
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
authors: Yuyu
authors: Y
authors: Niu
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Kunshan
authors: K
authors: Zhang
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.
authors: Yu
authors: Y
authors: Kang
authors: Dept. Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095 USA.
authors: Weihong
authors: W
authors: Ge
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Xiaojing
authors: X
authors: Liu
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.|Shanghai Huadong Hospital, Shanghai, 200040, China.
authors: Enfeng
authors: E
authors: Zhao
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Chencheng
authors: C
authors: Wang
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Shaoyun
authors: S
authors: Lin
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Bo
authors: B
authors: Jing
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.
authors: Chenyang
authors: C
authors: Si
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.|Dept. Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095 USA.
authors: Quan
authors: Q
authors: Lin
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.|Dept. Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095 USA.
authors: Xiaoying
authors: X
authors: Chen
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Haijun
authors: H
authors: Lin
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.
authors: Xiuqiong
authors: X
authors: Pu
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Yingying
authors: Y
authors: Wang
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Binlian
authors: B
authors: Qin
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.
authors: Fang
authors: F
authors: Wang
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
authors: Hong
authors: H
authors: Wang
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
authors: Wei
authors: W
authors: Si
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Jing
authors: J
authors: Zhou
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
authors: Tao
authors: T
authors: Tan
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
authors: Tianqing
authors: T
authors: Li
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
authors: Shaohui
authors: S
authors: Ji
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Zhigang
authors: Z
authors: Xue
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Yuping
authors: Y
authors: Luo
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Liming
authors: L
authors: Cheng
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors: Qi
authors: Q
authors: Zhou
authors: Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
authors: Siguang
authors: S
authors: Li
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China.|Dept. Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095 USA.
authors: Yi Eve
authors: YE
authors: Sun
authors: Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China.|Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China.|Life Science and Technology, Kunming University of Science and Technology, Kunming, 650224, China.
authors: Weizhi
authors: W
authors: Ji
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008252:Macaca fascicularis / Q000235:genetics*; D008253:Macaca mulatta / Q000235:genetics*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D051783:Methyl-CpG-Binding Protein 2; D015534:Trans-Activators; D004720:Endonucleases