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TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys

文献类型:期刊论文

作者Liu HL1,2; Chen YC1,3,4; Niu YY1,3,4; Zhang KS2; Kang Y1,3; Ge WH6; Liu XJ2; Zhao EF2,8; Wang CC1,2; Lin SY2
刊名CELL STEM CELL
出版日期2014
卷号14期号:3页码:323-328
通讯作者siguangli@163.com ; ysun@mednet.ucla.edu ; wji@kbimed.com
英文摘要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.
收录类别SCI
资助信息This work was supported by the Major State Basic Research Development Program of China(973 Program) (No. 2012CBA01300, 2012CB966900, 2010CB945202, and 2011CB965103), the National High Technology Research and Development Program of China (863 Program) (No. 2012AA020701), Yunnan Innovation Talents of Science and Technology (No. 2012HA013), the National Natural Science Foundation of China (31271599, U1302227, 31301058, 90919057, 31271371, and 91319309), Key program for the basic research of the science and technology commission of Shanghai (13JC1407102), ‘‘Western Light’’ Talents Training Program of CAS and Yunnan Academic Leaders and Reserve Personnel, and Young Talents Training Program of Tongji University. We also acknowledge grants from NIH (P01 GM081621-01A1 and 1R01MH082068-01A2) and CIRM (RB3-02129) to Y.E.S. and the Transcriptome and Epigenetics Core of Center for Study of Opioid Receptors and Drugs of Abuse (CSORDA center grant: NIH-P50DA005010) and Intellectual and Developmental Disabilities Research Center (IDDRC center grant: NIH-P30HD004612) at UCLA.
语种英语
WOS记录号WOS:000332533400009
公开日期2014-04-11
源URL[http://159.226.149.42:8088/handle/152453/7838]  
专题昆明动物研究所_生殖与发育生物学
作者单位1.Yunnan Key Laboratory of Primate Biomedical Research, Kunming, 650500, China
2.Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China
3.Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming, 650500, China
4.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China
5.State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
6.Department of Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095, USA
7.Life Science and Technology, Kunming University of Science and Technology, Kunming, 650224, China
8.Shanghai Huadong Hospital, Shanghai, 200040, China
推荐引用方式
GB/T 7714
Liu HL,Chen YC,Niu YY,et al. TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys[J]. CELL STEM CELL,2014,14(3):323-328.
APA Liu HL.,Chen YC.,Niu YY.,Zhang KS.,Kang Y.,...&Ji WZ[*].(2014).TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys.CELL STEM CELL,14(3),323-328.
MLA Liu HL,et al."TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys".CELL STEM CELL 14.3(2014):323-328.

入库方式: OAI收割

来源:昆明动物研究所

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