Generation of a monkey with MECP2 mutations by TALEN-based gene targeting.
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.
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Zhen
Z
Liu
Xue
X
Zhou
Ying
Y
Zhu
Zhi-Fang
ZF
Chen
Bin
B
Yu
Yan
Y
Wang
Chen-Chen
CC
Zhang
Yan-Hong
YH
Nie
Xiao
X
Sang
Yi-Jun
YJ
Cai
Yue-Fang
YF
Zhang
Chen
C
Zhang
Wen-Hao
WH
Zhou
Qiang
Q
Sun
Zilong
Z
Qiu
D000818:Animals; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005307:Fertilization in Vitro; D018390:Gene Targeting / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D008845:Microinjections; D009154:Mutation / Q000235:genetics*; D009865:Oocytes; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015053:Zygote / Q000502:physiology
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D014157:Transcription Factors; D004720:Endonucleases