机构：[1]Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science andTechnology, Kunming 650500, China[2]Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China[3]Yunnan Provincial Academy of Science and Technology, Kunming 650051, China[4]Department of Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095, USA[5]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province,Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China[6]Department of Radiology and BRIC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA[7]Key Laboratory for NeuroInformation of the Ministry of Education, School of Life Science and Technology, University of Electronic Scienceand Technology of China, Chengdu 625014, China[8]Department of Medical Imaging, the First Affiliated Hospital, Kunming Medical University, Kunming 650032, China医技科室医学影像中心昆明医科大学附属第一医院[9]The First People’s Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology,Kunming 650032, China医技科室医学影像中心昆明医科大学附属第一医院云南省第一人民医院[10]Department of Pediatrics, Peking University First Hospital, Beijing 100034, China[11]National Laboratory of Pattern Recognition, Brainnetome Center, Institute of Automation, Chinese Academy of Sciences,Beijing 100190, China云南省第一人民医院[12]Kunming Enovate Institute of Bioscience, Kunming 650000, China
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.
基金：
National Key Research and Development Program [2016YFA0101401, 2016YFA0100800]; National & Provincial Natural Science Foundation of China [U1602224, U1302227, 31571534, 2015FA037, 91319309, 31450110428, 31620103904, 2013HB133, 13JC1407102]; National Institute of Child Health Development of the NIH [U54HD087101-01]
第一作者机构：[1]Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science andTechnology, Kunming 650500, China[3]Yunnan Provincial Academy of Science and Technology, Kunming 650051, China[12]Kunming Enovate Institute of Bioscience, Kunming 650000, China
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通讯作者：
推荐引用方式(GB/T 7714)：
Yongchang Chen,Juehua Yu,Yuyu Niu,et al.Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys[J].CELL.2017,169(5):945-+.doi:10.1016/j.cell.2017.04.035.
APA：
Yongchang Chen,Juehua Yu,Yuyu Niu,Dongdong Qin,Hailiang Liu...&Yi Eve Sun.(2017).Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys.CELL,169,(5)
MLA：
Yongchang Chen,et al."Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys".CELL 169..5(2017):945-+
生物