TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys

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• 作者：Hailiang Liu¹ ; ² ; ⁹ ; Yongchang Chen¹ ; ³ ; ⁴ ; ⁹ ; Yuyu Niu¹ ; ³ ; ⁴ ; ⁹ ; Kunshan Zhang² ; ⁹ ; Yu Kang¹ ; ³ ; Weihong Ge⁶ ; Xiaojing Liu² ; Enfeng Zhao² ; ⁸ ; Chencheng Wang² ; Shaoyun Lin² ; Bo Jing² ; Chenyang Si¹ ; ³ ; Quan Lin² ; ⁶ ; Xiaoying Chen² ; ⁶ ; Haijun Lin² ; Xiuqiong Pu¹ ; ³ ; Yingying Wang² ; Binlian Qin² ; Fang Wang¹ ; ³ ; Hong Wang¹ ; ³ ; ⁴ ; Wei Si¹ ; ³ ; ⁴ ; Jing Zhou² ; Tao Tan¹ ; ³ ; ⁴ ; Tianqing Li¹ ; ³ ; ⁴ ; Shaohui Ji¹ ; ³ ; ⁴ ; Zhigang Xue² ; Yuping Luo² ; Liming Cheng² ; Qi Zhou⁵ ; Siguang Li² ; ^{siguangli@163.com" class="auth_mail} ; Yi Eve Sun¹ ; ² ; ⁶ ; ^{ysun@mednet.ucla.edu" class="auth_mail} ; Weizhi Ji¹ ; ³ ; ⁷ ; ^{wji@kbimed.com" class="auth_mail}
• 刊名：Cell Stem Cell
• 出版年：6 March, 2014
• 年：2014
• 卷：14
• 期：3
• 页码：323-328
• 全文大小：1337 K

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Summary

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聽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.