{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:19:11Z","timestamp":1758673151331,"version":"3.44.0"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"crossref","award":["24K09301"],"award-info":[{"award-number":["24K09301"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Santen Pharmaceutical Co., Ltd.","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Teika Pharmaceutical Co., Ltd.","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Johnson & Johnson Surgical Vision, Inc.","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>The rd6 mouse model, characterized by retinal degeneration due to an <jats:italic><jats:italic>Mfrp<\/jats:italic><\/jats:italic> mutation, has been widely studied. However, we identified a subset of rd6 mice that developed severe non-rhegmatogenous retinal detachment (rd6-RD), suggesting the presence of additional genetic factors. This study aimed to characterize the retinal phenotype of rd6-RD mice and identify potential causative genetic mutations.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We performed optical coherence tomography, fundus imaging, electroretinography, and histological analysis to compare retinal structures and functions between rd6, rd6-RD, and C57BL\/6J mice. Whole-genome sequencing was conducted to identify potential mutations associated with the retinal detachment phenotype.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Optical coherence tomography revealed retinal detachment in rd6-RD mice as early as 4 weeks old, with complete loss of the outer nuclear layer by 6 weeks. Fundus examination at 11 weeks showed pale fundi and narrowed, whitened retinal vessels in rd6-RD mice, distinct from rd6 mice. On electroretinography, rd6-RD mice displayed significantly diminished a- and b-wave amplitudes, with no detectable responses by 10 weeks. Histological analysis confirmed severe outer retinal degeneration and disappearance of the outer layers in rd6-RD mice. Whole-genome sequencing identified a missense R560C mutation in <jats:italic><jats:italic>Pde6b<\/jats:italic><\/jats:italic>, corresponding to the <jats:italic><jats:italic>Pde6b<\/jats:italic><\/jats:italic><jats:sup><jats:italic>rd10<\/jats:italic><\/jats:sup> mutation, in rd6-RD mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>A subset of rd6 mice exhibited severe retinal detachment and outer retinal degeneration, distinct from the previously characterized <jats:italic><jats:italic>Mfrp<\/jats:italic><\/jats:italic>-related phenotype. The identification of the <jats:italic><jats:italic>Pde6b<\/jats:italic><\/jats:italic><jats:sup><jats:italic>rd10<\/jats:italic><\/jats:sup> mutation suggests that these mice possess a dual-mutant genotype (<jats:italic><jats:italic>Mfrp<\/jats:italic><\/jats:italic><jats:sup><jats:italic>rd6<\/jats:italic><\/jats:sup> and <jats:italic><jats:italic>Pde6b<\/jats:italic><\/jats:italic><jats:sup><jats:italic>rd10<\/jats:italic><\/jats:sup>), exacerbating retinal degeneration. These findings highlight the importance of genetic verification in commercially available mouse models and provide new insights into the genetic complexity of inherited retinal degenerations.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0332446","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T17:33:43Z","timestamp":1758648823000},"page":"e0332446","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of coexisting Mfrprd6 and Pde6brd10 mutations causing spontaneous retinal detachment in commercially available rd6 mice"],"prefix":"10.1371","volume":"20","author":[{"given":"Asaka Lee","family":"Shiozawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maika Hosoi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8673-677X","authenticated-orcid":true,"given":"Yusuke","family":"Shiozawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Miyagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiki","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mashito","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2910-3797","authenticated-orcid":true,"given":"Takashi","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7467-6746","authenticated-orcid":true,"given":"Tsutomu","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"issue":"9549","key":"pone.0332446.ref001","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"DT Hartong","year":"2006","journal-title":"Lancet"},{"issue":"3","key":"pone.0332446.ref002","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0002-9394(84)90636-6","article-title":"Prevalence of retinitis pigmentosa in Maine","volume":"97","author":"CH Bunker","year":"1984","journal-title":"Am J Ophthalmol"},{"issue":"1","key":"pone.0332446.ref003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0021-5155(96)00019-6","article-title":"Multicenter genetic study of retinitis pigmentosa in Japan: II. 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