Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development

查看全文 作　　者：Lei [1,2,3]Shi;Xin [1,2,3,4]Luo;Jin [1,2,3,4]Jiang;Yongchang [5]chen;Cirong [1]Liu;Ting [1,2,3,4]Hu;Min [1]Li;Qiang [1]Lin;Yanjiao [1]Li;Jun [1]Huang;Hong [5]Wang;Yuyu [5]Niu;Yundi [6]Shi;Martin [6,7]Styner;Jianhong [8]Wang;Yi [9]Lu;Xuejin [9]Sun;Hualin [10]Yu;Weizhi [5]Ji;Bing [1,2,3]Su

机构地区：[1]State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China;[10]Department of Minimally Invasive Neurosurgery,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China;[2]Primate Research Center,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China;[3]Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming 650223,China;[4]Kunming College of Life Science,University of Chinese Academy of Sciences,Beijing 100101,China;[5]Yunnan Key Laboratory of Primate Biomedical Research,Institute of Primate Translation Medicine,Kunming University of Science and Technology,Kunming 650500,China;[6]Department of Psychiatry,University of North Carolina,Chapel Hill,NC 27599-7160,USA;[7]Department of Computer Science,University of North Carolina,Chapel Hill,NC 27599-7160,USA;[8]Key Laboratory of Animal Models and Human Disease Mechanisms,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China;[9]Department of Medical Imaging,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China

出　　处：《National Science Review》索引2019年第6卷第3期,共14页

基　　金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000to B.S.);the National Natural Science Foundation of China(31730088 and 31621062 to B.S.);the Youth Innovation Promotion Association of CAS(to L.S.) 摘　　要：Brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive.Here,we successfully generated 11 transgenic rhesus monkeys(8 first-generation and 3 second-generation)carrying human copies of MCPH1,an important gene for brain development and brain evolution.Brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation,resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys,similar to the known evolutionary change of developmental delay(neoteny)in humans.Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes,providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys.More importantly,the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task.The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits. 关键词：HUMAN evolution BRAIN development MCPH1 TRANSGENIC MONKEY neoteny COGNITION

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Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development

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