TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys.
TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys.
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DOI：
10.1016/j.stem.2014.01.018
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发表时间：
2014-03-06
期刊：
影响因子：
23.9
通讯作者：
Ji, Weizhi
中科院分区：
文献类型：
--
作者：
Liu, Hailiang;Chen, Yongchang;Niu, Yuyu;Zhang, Kunshan;Kang, Yu;Ge, Weihong;Liu, Xiaojing;Zhao, Enfeng;Wang, Chencheng;Lin, Shaoyun;Jing, Bo;Si, Chenyang;Lin, Quan;Chen, Xiaoying;Lin, Haijun;Pu, Xiuqiong;Wang, Yingying;Qin, Binlian;Wang, Fang;Wang, Hong;Si, Wei;Zhou, Jing;Tan, Tao;Li, Tianqing;Ji, Shaohui;Xue, Zhigang;Luo, Yuping;Cheng, Liming;Zhou, Qi;Li, Siguang;Sun, Yi Eve;Ji, Weizhi
基因编辑技术的最新进展已经引入了在非人灵长类动物中应用诱变方法来模拟人类发育和疾病的潜力。在这里，我们报告成功的TALEN介导的X-连锁，Rett综合征（RTT）基因，甲基-CpG结合蛋白2（MECP 2），在恒河猴和食蟹猴的诱变。将靶向MECP 2的TALEN质粒显微注射到恒河猴和食蟹猴受精卵中导致MECP 2的有效基因编辑，而没有检测到脱靶诱变。在包括睾丸在内的各种组织中携带MECP 2突变的雄性恒河猴（2）和食蟹猴（1）胎儿在妊娠中期流产，与人类RTT相关的雄性胚胎致死性一致。一只雌性食蟹猴在妊娠162天后活产，外周组织中存在大量MECP 2突变。我们的结论是，TALEN介导的突变可以成为非人灵长类动物人类疾病遗传建模的有效工具。
Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in non-human primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett Syndrome (RTT) gene, the 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 mid-gestation, 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 non-human primates.
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影响因子：
16
作者：
Skene, Peter J.;Illingworth, Robert S.;Webb, Shaun;Kerr, Alastair R. W.;James, Keith D.;Turner, Daniel J.;Andrews, Rob;Bird, Adrian P.
通讯作者：
Bird, Adrian P.
影响因子：
5.8
作者：
Grau, Jan;Boch, Jens;Posch, Stefan
通讯作者：
Posch, Stefan
影响因子：
46.9
作者：
Cho, Seung Woo;Kim, Sojung;Kim, Jin-Soo
通讯作者：
Kim, Jin-Soo
DOI：
10.1111/j.1651-2227.1985.tb10993.x
发表时间：
1985-01-01
期刊：
ACTA PAEDIATRICA SCANDINAVICA
影响因子：
--
作者：
HAGBERG, B
通讯作者：
HAGBERG, B
影响因子：
56.9
作者：
Chan, AWS;Chong, KY;Schatten, G
通讯作者：
Schatten, G