Generation of a monkey with MECP2 mutations by TALEN-based gene targeting
Generation of a monkey with MECP2 mutations by TALEN-based gene targeting
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DOI：
10.1007/s12264-014-1434-8
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发表时间：
2014-06-01
影响因子：
5.6
通讯作者：
Qiu, Zilong
中科院分区：
文献类型：
--
作者：
Liu, Zhen;Zhou, Xue;Qiu, Zilong
模式生物中的基因编辑为大脑发育和疾病提供了重要的见解。在这里，我们报告了使用转录激活因子样效应核酸酶（TALEN）介导的基因靶向产生携带MECP2突变的食蟹猴（食蟹猴）。将TALENs mRNA注射到通过体外受精获得的猴受精卵中并将胚胎移植到代孕猴中后，我们获得了一只雄性新生猴，其在各种组织中具有由移码突变引起的MECP 2缺失。携带MECP2突变的猴子在出生后未能存活，这是由于TALEN的毒性或MECP2对神经发育的关键要求。在猴子的大脑中，MeCP2蛋白质的水平基本上被耗尽。这项研究证明了通过位点特异性基因编辑方法在非人灵长类动物中引入基因突变的可行性。
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.