Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室

	Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys
	Chen YC[]1,3,12,13,14; Yu JH 2,13; Li G 6; Hu YZ 5; Wang JJ 7; Lu Y 8; Hu XT 5; Ma YY 1,3; Niu YY 1,3,12,13; Ji WZ[]1,3,12
刊名	Cell
	2017
卷号	169 期号:X 页码:945–955
其他题名	chenyc@lpbr.cn;wji@lpbr.cn;ysun@mednet.ucla.edu
英文摘要	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.
资助信息	This work was supported by the National Key Research and Development Program (2016YFA0101401 and 2016YFA0100800), the National & Provincial Natural Science Foundation of China (U1602224, U1302227, 31571534, 2015FA037, 91319309, 31450110428, 31620103904, 2013HB133, and 13JC1407102), and the National Institute of Child Health Development of the NIH (U54HD087101-01).
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/11629]
专题	昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_神经系统编码
作者单位	1.Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, 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 Science and Technology of China, Chengdu 625014, China 8.Department of Medical Imaging, the First Affiliated Hospital, Kunming Medical University, Kunming 650032, China 9.The First People’s Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China 10.Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
推荐引用方式 GB/T 7714	Chen YC[*],Yu JH,Li G,et al. Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys[J]. Cell,2017,169(X):945–955.
APA	Chen YC[*].,Yu JH.,Li G.,Hu YZ.,Wang JJ.,...&Liu HL.(2017).Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys.Cell,169(X),945–955.
MLA	Chen YC[*],et al."Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys".Cell 169.X(2017):945–955.