globalchange  > 气候变化与战略
DOI: 10.1016/j.scib.2020.09.008
论文题名:
Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina
作者: Li S.; Hu Y.; Li Y.; Hu M.; Wang W.; Ma Y.; Cai Y.; Wei M.; Yao Y.; Wang Y.; Dong K.; Gu Y.; Zhao H.; Bao J.; Qiu Z.; Zhang M.; Hu X.; Xue T.
刊名: Science Bulletin
ISSN: 20959273
出版年: 2021
卷: 66, 期:4
起始页码: 374
结束页码: 385
语种: 英语
中文关键词: Disease model ; Gene editing ; Nonhuman primate model ; Retinitis pigmentosa ; Rhodopsin ; SaCas9
英文关键词: Mammals ; Ophthalmology ; Viruses ; Adeno-associated virus ; Human disease ; Non-human primate ; Photoresponses ; Retinal degenerative disease ; Retinitis pigmentosa ; Rho proteins ; Subcellular structure ; Genes
英文摘要: 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 rodents. Therefore, 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 future. Here 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 RP. Through a series of studies, we were able to demonstrate successful somatic editing of the RHO gene and reduced RHO protein expression. More importantly, the mutant macaque retinae displayed clinical RP phenotypes, including photoreceptor degeneration, retinal thinning, abnormal rod subcellular structures, and reduced photoresponse. Therefore, 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. © 2020 Science China Press
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/170316
Appears in Collections:气候变化与战略

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作者单位: Hefei National Laboratory for Physical Sciences at the Microscale, Eye Center, The First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Second People's Hospital of Yunnan Province, Yunnan Eye Institute, Key Laboratory of Yunnan Province for the Prevention and Treatment of Ophthalmology, Kunming, Yunnan 650223, China; Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China; Department of Biological and Environmental Engineering, Hefei University, Hefei, 230601, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China; Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, 200031, China; National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China; Neurodegenerative Disorder Research Center, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, 230026, China

Recommended Citation:
Li S.,Hu Y.,Li Y.,et al. Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina[J]. Science Bulletin,2021-01-01,66(4)
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