检索结果-南通市图书馆

Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina

Science Bulletin 2021年第4期66卷 374-385,M0004页

作者： Shouzhen Li Yingzhou Hu Yunqin Li Min Hu Wenchao Wang Yuqian Ma Yuan Cai Min Wei Yichuan Yao Yun Wang Kai Dong Yonghao Gu Huan Zhao Jin Bao Zilong Qiu Mei Zhanga Xintian Hu Tian Xue Hefei National Laboratory for Physical Sciences at the Microscale Eye Center at The First Affiliated Hospital of USTCSchool of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Key Laboratory of Animal models and Human Disease Mechanisms of Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Second People's Hospital of Yunnan Province Yunnan Eye InstituteKey Laboratory of Yunnan Province for the Prevention and Treatment of OphthalmologyKunming 650223China Kunming primate Research Center Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Department of Biological and Environmental Engineering Hefei UniversityHefei 230601China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Institute of Neuroscience State Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China National Research Facility for Phenotypic&Genetic Analysis of model Animals(primate Facility) Kunming Institute of ZoologyChinese Academy of SciencesKunming 650107China Neurodegenerative Disorder Research Center CAS Key Laboratory of Brain Function and DiseaseUniversity of Science and Technology of ChinaHefei 230026China

Retinitis pigmentosa(RP)is a form of inherited retinal degenerative diseases that ultimately involves the macula,which is present in primates but not in the ***,creating nonhuman primate(NHP)models of RP is of critical importance to study its mechanism of pathogenesis and to evaluate potential therapeutic options in the *** we applied adeno-associated virus(AAV)-delivered CRISPR/SaCas9 technology to knockout the RHO gene in the retinae of the adult rhesus macaque(Macaca mulatta)to investigate the hypothesis whether non-germline mutation of the RHO gene is sufficient to recapitulate *** a series of studies,we were able to demonstrate successful somatic editing of the RHO gene and reduced RHO protein *** importantly,the mutant macaque retinae displayed clinical RP phenotypes,including photoreceptor degeneration,retinal thinning,abnormal rod subcellular structures,and reduced ***,we suggest somatic editing of the RHO gene is able to phenocopy RP,and the reduced time span in generating NHP mutant accelerates RP research and expands the utility of NHP model for human disease study.

关键词： nonhuman primate model Retinitis pigmentosa Rhodopsin Disease model Gene editing SaCas9

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys

引用

Science Bulletin 2021年第9期66卷 937-946,M0004页

作者： Shi-Hao Wu Xiao Li Dong-Dong Qin Lin-Heng Zhang Tian-Lin Cheng Zhi-Fang Chen Bin-Bin Nie Xiao-Feng Ren Jing Wu Wen-Chao Wang Ying-Zhou Hu Yi-Lin Gu Long-Bao Lv Yong Yin Xin-Tian Hu Zi-Long Qiu Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Key Laboratory of Primate NeurobiologyChinese Academy of SciencesShanghai 200031China Key Laboratory of Animal models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China National Resource Center for Non-Human primates Kunming Primate Research Centerand National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunming 650107China Kunming College of Life Science University of the Chinese Academy of SciencesKunming 650204China Beijing Engineering Research Center of Radiographic Techniques and Equipment Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China Department of Rehabilitation Medicine the Second People's Hospital of Yunnan ProvinceKunming 650021China Yunnan University of Chinese Medicine Kunming 650500China Academy for Engineering&Technology Fudan UniversityShanghai 200433China National Clinical Research Center for Aging and Medicine Huashan HospitalFudan UniversityShanghai 200040China

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 *** 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(sg RNAs)targeting *** comparison to monkeys injected with AAV-Sa Cas9 alone(n=4),numerous autistic-like behavioral abnormalities were identified in the AAV-Sa Cas9-sg MECP2-injected monkeys(n=7),including social interaction deficits,abnormal sleep patterns,insensitivity to aversive stimuli,abnormal hand motions,and defective social reward ***,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 *** 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.

关键词： Autism spectrum disorders nonhuman primate model Disease model Gene-editing

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：