Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype
经由在成年猴子大脑的联系 Adeno 的交付病毒的 CRISPR/Cas9 系统的共同编辑的 PINK1 和 DJ-1 基因得到古典 Parkinsonian 显型作者机构：Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan ProvinceKunming Institute of ZoologyChinese Academy of Sciences650223 KunmingChina Institute of NeuroscienceCAS Key Laboratory of Primate NeurobiologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Institutes of Physical Science and Information TechnologyAnhui UniversityHefei 230601China Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China National Resource Center for Non-human PrimatesKunming Primate Research Centerand National Research Facility for Phenotypic and Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of Sciences650107 KunmingChina Diagnostic Radiology Department920 Hospital of the Joint Logistics Support Force of the PLAKunming 650032China Ultrasound diagnosis Department920 Hospital of the Joint Logistics Support Force of the PLAKunming 650032China Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Department of Rehabilitation MedicineThe Second People’s Hospital of Yunnan ProvinceKunming 650021China National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghai 200433China
出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)
年 卷 期：2021年第37卷第9期
页 面：1271-1288页
核心收录：
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金：This work was supported by the National Key R&D Program of China(2018YFA0801403) the Key-Area Research and Development Program of Guangdong Province(2019B030335001) the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32060200) the National Program for Key Basic Research Projects(973 Program:2015CB755605) the National Natural Science Foundation of China(81471312,81771387,81460352,81500983,31700897,31700910,31800901,31625013,and 91732302) the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(2017FB109,2018FB052,2018FB053,2019FA007,and 202001AT070130) Chinese Academy of Sciences"Light of West China"Program,Shanghai Brain-Intelligence Project from Science and Technology Commission of Shanghai Municipality(16JC1420501) Shanghai Municipal Science and Technology Major Project(2018SHZDZX05) Open Large Infrastructure Research of Chinese Academy of Sciences,and China Postdoctoral Science Foundation(2018M631105)
主 题：Parkinson’s disease Monkey Adeno-associated virus-delivered CRISPR/Cas9 PINK1 DJ-1 Parkinsonian phenotype
摘 要：Whether direct manipulation of Parkinson’s disease(PD)risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved ***,we used an adeno-associated virus serotype 9(AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras(SNs)of two monkey groups:an old group and a middle-aged *** the operation,the old group exhibited all the classic PD symptoms,including bradykinesia,tremor,and postural instability,accompanied by key pathological hallmarks of PD,such as severe nigral dopaminergic neuron loss(64%)and evidentα-synuclein pathology in the gene-edited *** contrast,the phenotype of their middle-aged counterparts,which also showed clear PD symptoms and pathological hallmarks,were less *** addition to the higher final total PD scores and more severe pathological changes,the old group were also more susceptible to gene editing by showing a faster process of PD *** results suggested that both genetic and aging factors played important roles in the development of PD in the *** together,this system can effectively develop a large number of genetically-edited PD monkeys in a short time(6–10 months),and thus provides a practical transgenic monkey model for future PD studies.
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