| Literature DB >> 24529597 |
Hailiang Liu1,2, Yongchang Chen1,3,4, Yuyu Niu1,3,4, Kunshan Zhang2, Yu Kang1,3, Weihong Ge5, Xiaojing Liu2, Enfeng Zhao2,6, Chencheng Wang2, Shaoyun Lin2, Bo Jing2, Chenyang Si1,3, Quan Lin2,5, Xiaoying Chen2,5, 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 Zhou7, Siguang Li2, Yi Eve Sun1,2,5, Weizhi Ji1,3,8.
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 24529597 PMCID： PMC4024384 DOI： 10.1016/j.stem.2014.01.018
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633