气候变化领域集成服务门户(CCPortal): Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys

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DOI	10.1016/j.scib.2020.12.017
	Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys
	Wu S.-H.; Li X.; Qin D.-D.; Zhang L.-H.; Cheng T.-L.; Chen Z.-F.; Nie B.-B.; Ren X.-F.; Wu J.; Wang W.-C.; Hu Y.-Z.; Gu Y.-L.; Lv L.-B.; Yin Y.; Hu X.-T.; Qiu Z.-L.
发表日期	2021
ISSN	20959273
英文摘要	Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders, whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined. Here we induced genetic mutations in MECP2, a critical gene linked to Rett syndrome (RTT) and autism spectrum disorders (ASD), in the hippocampus (DG and CA1–4) of adolescent rhesus monkeys (Macaca mulatta) in vivo via adeno-associated virus (AAV)-delivered Staphylococcus aureus Cas9 with small guide RNAs (sgRNAs) targeting MECP2. In comparison to monkeys injected with AAV-SaCas9 alone (n = 4), numerous autistic-like behavioral abnormalities were identified in the AAV-SaCas9-sgMECP2-injected monkeys (n = 7), including social interaction deficits, abnormal sleep patterns, insensitivity to aversive stimuli, abnormal hand motions, and defective social reward behaviors. Furthermore, some aspects of ASD and RTT, such as stereotypic behaviors, did not appear in the MECP2 gene-edited monkeys, suggesting that different brain areas likely contribute to distinct ASD symptoms. This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates, paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development. © 2020 Science China Press
关键词	Autism spectrum disorders Disease model Gene-editing Nonhuman primate model
英文关键词	Bacteria; Diseases; Mammals; Viruses; Adeno-associated virus; Autism spectrum disorders; Behavioral changes; Disease-causing gene; Genetic mutations; Non-human primate; Rapid generations; Social interactions; Genes
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207610
作者单位	Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai 200031, China; 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; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, China; Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, Yunnan 650204, China; Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China;...
推荐引用方式 GB/T 7714	Wu S.-H.,Li X.,Qin D.-D.,et al. Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys[J],2021.
APA	Wu S.-H..,Li X..,Qin D.-D..,Zhang L.-H..,Cheng T.-L..,...&Qiu Z.-L..(2021).Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys.Science Bulletin.
MLA	Wu S.-H.,et al."Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys".Science Bulletin (2021).