气候变化领域集成服务门户(CCPortal): Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina

CCPortal

DOI	10.1016/j.scib.2020.09.008
	Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina
	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.
发表日期	2021
ISSN	20959273
起始页码	374
结束页码	385
卷号	66 期号:4
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
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
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/207472
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...
推荐引用方式 GB/T 7714	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],2021,66(4).
APA	Li S..,Hu Y..,Li Y..,Hu M..,Wang W..,...&Xue T..(2021).Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina.Science Bulletin,66(4).
MLA	Li S.,et al."Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina".Science Bulletin 66.4(2021).