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

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

May 16, 2014

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.

Authors: Zhen LiuXue ZhouYing ZhuZhi-Fang ChenBin YuYan WangChen-Chen ZhangYan-Hong NieXiao SangYi-Jun CaiYue-Fang ZhangChen ZhangWen-Hao ZhouQiang Sun Zilong Qiu

Influence Factor: 2.624

Citation: Neurosci Bull 30, 381-386 (2014).

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