Generation of a monkey with MECP2 mutations by TALEN-based gene targeting
1Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2Department of Neonatology, Children’s Hospital of Fudan University, S hanghai 201102, China
3State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China
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
