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However, the underlying molecular mechanisms remain elusive due to a lack of suitable disease models. We developed two independent Impg2 knockout (KO) mouse models using the CRISPR\/Cas9 technique to assess the in vivo functions of Impg2 in the retina. Impg2 ablation in mice recapitulated the RP phenotypes of patients, including an attenuated electroretinogram (ERG) response and the progressive degeneration of photoreceptors. The histopathological examination of Impg2-KO mice revealed irregularly arranged rod cells and mislocalized rhodopsin protein in the inner segment at 6\u00a0months of age. In addition to the pathological changes in rod cells, cone cells were also affected in KO retinas. KO retinas exhibited progressive cone cell death and impaired cone cell elongation. Further immunoblotting analysis revealed increased levels of endoplasmic reticulum (ER) stress-related proteins, including C\/EBP homologous protein (CHOP), immunoglobulin heavy-chain-binding protein (BIP) and protein disulfide isomerase (PDI), in Impg2-KO mouse retinas. Increased gliosis and apoptotic cell death were also observed in the KO retinas. As autophagy is closely associated with ER stress, we then checked whether autophagy was disturbed in Impg2-KO mouse retinas. The results showed that autophagy was impaired in KO retinas, as revealed by the increased accumulation of SQSTM1 and other proteins involved in autophagy. Our results demonstrate the essential roles of Impg2 in the retina, and this study provides novel models for mechanistic investigations and development of therapies for RP caused by IMPG2 mutations.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa062","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T11:12:14Z","timestamp":1585653134000},"page":"1624-1634","source":"Crossref","is-referenced-by-count":22,"title":["Deletion of the Impg2 gene causes the degeneration of rod and cone cells in mice"],"prefix":"10.1093","volume":"29","author":[{"given":"Huijuan","family":"Xu","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"},{"name":"Chengdu Institute of Biology, Sichuan Translational Medicine Research Hospital, Chinese Academy of Sciences, Chengdu 610072, Sichuan, China"},{"name":"Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People\u2019s Hospital, Chengdu 610072, Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Qu","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"},{"name":"Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People\u2019s Hospital, Chengdu 610072, Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gan","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuanxiang","family":"Sun","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junkai","family":"Tan","sequence":"first","affiliation":[{"name":"Xiamen Eye Center, Xiamen University, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Liu","sequence":"first","affiliation":[{"name":"Xiamen Eye Center, Xiamen University, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Jiang","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"},{"name":"Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People\u2019s Hospital, Chengdu 610072, Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanli","family":"Tian","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Liu","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhang","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeming","family":"Yang","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"},{"name":"Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People\u2019s Hospital, Chengdu 610072, Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2531-7552","authenticated-orcid":false,"given":"Xianjun","family":"Zhu","sequence":"first","affiliation":[{"name":"The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China"},{"name":"Chengdu Institute of Biology, Sichuan Translational Medicine Research Hospital, Chinese Academy of Sciences, Chengdu 610072, Sichuan, China"},{"name":"Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People\u2019s Hospital, Chengdu 610072, Sichuan China"},{"name":"Research Unit for Blindness 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"2020062904235215400_ref1","first-page":"195","article-title":"The interphotoreceptor matrix\u2014functions and possible role in hereditary retinal degenerations","volume":"190","author":"Bridges","year":"1985","journal-title":"Prog. 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