globalchange  > 气候变化与战略
DOI: 10.1016/j.scib.2020.12.017
Title:
Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys
Author: 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.
Source Publication: Science Bulletin
ISSN: 20959273
Publishing Year: 2021
Language: 英语
keyword in Chinese: Autism spectrum disorders ; Disease model ; Gene-editing ; Nonhuman primate model
Keyword: 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
English Abstract: 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
Citation statistics:
Document Type: 期刊论文
Identifier: http://119.78.100.158/handle/2HF3EXSE/170444
Appears in Collections:气候变化与战略

Files in This Item:

There are no files associated with this item.


Affiliation: 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; School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 100049, China; Department of Rehabilitation Medicine, the Second People's Hospital of Yunnan Province, Kunming 650021, China; Yunnan University of Chinese Medicine, Kunming 650500, China; Academy for Engineering & Technology, Fudan University, Shanghai 200433, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China

Recommended Citation:
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]. Science Bulletin,2021-01-01
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Wu S.-H.]'s Articles
[Li X.]'s Articles
[Qin D.-D.]'s Articles
百度学术
Similar articles in Baidu Scholar
[Wu S.-H.]'s Articles
[Li X.]'s Articles
[Qin D.-D.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Wu S.-H.]‘s Articles
[Li X.]‘s Articles
[Qin D.-D.]‘s Articles
Related Copyright Policies
Null
收藏/分享
所有评论 (0)
暂无评论
 

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.