{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:55:06Z","timestamp":1782910506715,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200479"],"award-info":[{"award-number":["32200479"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2108085QC99"],"award-info":[{"award-number":["2108085QC99"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005063","name":"Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province","doi-asserted-by":"publisher","award":["2024AH030041"],"award-info":[{"award-number":["2024AH030041"]}],"id":[{"id":"10.13039\/501100005063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007924","name":"Bengbu Medical College","doi-asserted-by":"publisher","award":["2024bypy014"],"award-info":[{"award-number":["2024bypy014"]}],"id":[{"id":"10.13039\/501100007924","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The NR2E3\n                    <jats:sup>R311Q<\/jats:sup>\n                    mutation can lead to retinitis pigmentosa, enhanced S\u2010cone syndrome (ESCS), Goldmann\u2013Favre syndrome, and clumped pigmentary retinal degeneration. The relationship between this mutation and various recessive inherited retinal degenerative disorders is unclear and complicates clinical diagnosis and treatment. In this study, we generated a mouse strain carrying the NR2E3\n                    <jats:sup>R296Q<\/jats:sup>\n                    mutation using CRISPR\/Cas9 technology to simulate the NR2E3\n                    <jats:sup>R311Q<\/jats:sup>\n                    mutation in humans and investigate the influence of this missense mutation on the photoreceptor developmental profile and retinal maintenance. Retinal architecture and lamination were normal in NR2E3\n                    <jats:sup>R296Q<\/jats:sup>\n                    mice. Whorls and rosettes were not observed in the outer nuclear layer (ONL). Rod cell quantity developed normally, whereas a small amount of Rhodopsin was incorrectly located in the ONL. Blue cones were excessively produced at the dorsal retina, whereas green cone development was normal. Colocalization of Rhodopsin and Arrestin occurred in the retinas of NR2E3\n                    <jats:sup>R296Q<\/jats:sup>\n                    mice. Heterozygous NR2E3\n                    <jats:sup>+\/R296Q<\/jats:sup>\n                    mice showed no evident abnormalities in retinal structure or photoreceptor development. Retinas of NR2E3\n                    <jats:sup>R296Q<\/jats:sup>\n                    mice underwent progressive degeneration starting in the early postnatal stage, which manifested as reduced ONL thickness and outer segment fragmentation. The dorsal retina, where redundant blue cones are generated, degenerated in a more advanced manner. At the molecular level, NR2E3 bound directly to the\n                    <jats:italic>RXRG<\/jats:italic>\n                    promoter, whereas the NR2E3 R296Q mutation significantly impaired binding, resulting in significantly decreased\n                    <jats:italic>RXRG<\/jats:italic>\n                    mRNA and protein expressions. In summary, we developed a novel mouse model exhibiting an ESCS\u2010like phenotype, thus providing a novel NR2E3\u2010RXRG signaling pathway for modulating photoreceptor development and retinal maintenance.\n                  <\/jats:p>","DOI":"10.1096\/fj.202402980r","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T06:28:59Z","timestamp":1746253739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mouse\n                    <scp>\n                      NR2E3\n                      <sup>R296Q<\/sup>\n                    <\/scp>\n                    Mutation Disrupts Photoreceptor Developmental Paradigm and Leads to Early\u2010Onset Progressive Retinal Degeneration by Suppressing\n                    <scp>RXRG<\/scp>\n                    Signaling"],"prefix":"10.1096","volume":"39","author":[{"given":"Jiacheng","family":"Jin","sequence":"first","affiliation":[{"name":"School of Life Sciences, Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment Bengbu Medical University  Bengbu Anhui P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment Bengbu Medical University  Bengbu Anhui P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjiu","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment Bengbu Medical University  Bengbu Anhui P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanglun","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment Bengbu Medical University  Bengbu Anhui P.R. 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