| Literature DB >> 28525759 |
Yongchang Chen1, Juehua Yu2, Yuyu Niu3, Dongdong Qin4, Hailiang Liu2, Gang Li5, Yingzhou Hu4, Jiaojian Wang6, Yi Lu7, Yu Kang3, Yong Jiang8, Kunhua Wu8, Siguang Li2, Jingkuan Wei9, Jing He9, Junbang Wang2, Xiaojing Liu2, Yuping Luo2, Chenyang Si3, Raoxian Bai9, Kunshan Zhang2, Jie Liu2, Shaoyong Huang9, Zhenzhen Chen9, Shuang Wang9, Xiaoying Chen2, Xinhua Bao10, Qingping Zhang10, Fuxing Li2, Rui Geng2, Aibin Liang2, Dinggang Shen5, Tianzi Jiang11, Xintian Hu4, Yuanye Ma9, Weizhi Ji12, Yi Eve Sun13.
Abstract
Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT.Entities:
Keywords: MECP2; Rett syndrome; disease models; gene editing; male embryonic lethal; neurodevelopmental disorder; non-human primate
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Year: 2017 PMID： 28525759 PMCID： PMC5540256 DOI： 10.1016/j.cell.2017.04.035
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582