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Neuroscience Bulletin

, Volume 30, Issue 3, pp 381–386 | Cite as

Generation of a monkey with MECP2 mutations by TALEN-based gene targeting

  • Zhen Liu
  • Xue Zhou
  • Ying Zhu
  • Zhi-Fang Chen
  • Bin Yu
  • Yan Wang
  • Chen-Chen Zhang
  • Yan-Hong Nie
  • Xiao Sang
  • Yi-Jun Cai
  • Yue-Fang Zhang
  • Chen Zhang
  • Wen-Hao Zhou
  • Qiang SunEmail author
  • Zilong QiuEmail author
Report

Abstract

Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey (Macaca fascicularis) carrying MECP2 mutations using transcription activator-like effector nucleases (TALENs)-mediated gene targeting. After injecting TALENs mRNA into monkey zygotes achieved by in vitro fertilization and embryo transplantation into surrogate monkeys, we obtained one male newborn monkey with an MECP2 deletion caused by frameshifting mutation in various tissues. The monkey carrying the MECP2 mutation failed to survive after birth, due to either the toxicity of TALENs or the critical requirement of MECP2 for neural development. The level of MeCP2 protein was essentially depleted in the monkey’s brain. This study demonstrates the feasibility of introducing genetic mutations in non-human primates by site-specific gene-editing methods.

Keywords

monkey TALEN MeCP2 Rett syndrome 

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Zhen Liu
    • 1
  • Xue Zhou
    • 1
  • Ying Zhu
    • 1
  • Zhi-Fang Chen
    • 1
  • Bin Yu
    • 1
    • 2
  • Yan Wang
    • 1
  • Chen-Chen Zhang
    • 1
  • Yan-Hong Nie
    • 1
  • Xiao Sang
    • 1
    • 2
  • Yi-Jun Cai
    • 1
  • Yue-Fang Zhang
    • 1
  • Chen Zhang
    • 3
  • Wen-Hao Zhou
    • 2
  • Qiang Sun
    • 1
    Email author
  • Zilong Qiu
    • 1
    Email author
  1. 1.Institute of Neuroscience, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  2. 2.Department of NeonatologyChildren’s Hospital of Fudan UniversityShanghaiChina
  3. 3.State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences; PKU-IDG/McGovern Institute for Brain ResearchPeking UniversityBeijingChina

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