{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:00:28Z","timestamp":1791896428299,"version":"4.3.4"},"reference-count":57,"publisher":"Society for Neuroscience","issue":"13","license":[{"start":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T00:00:00Z","timestamp":1538092800000},"content-version":"vor","delay-in-days":227,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2018,3,28]]},"abstract":"<jats:p><jats:italic>C8ORF37<\/jats:italic>is a causative gene for three different clinical forms of incurable retinal degeneration. However, the completely unknown function of<jats:italic>C8ORF37<\/jats:italic>limits our understanding of the pathogenicity of<jats:italic>C8ORF37<\/jats:italic>mutations. Here, we performed a comprehensive phenotypic characterization of a<jats:italic>C8orf37<\/jats:italic>KO mouse line, generated using CRISPR\/Cas9 technology. Both<jats:italic>C8orf37<\/jats:italic>KO male and female mice exhibited progressive and simultaneous degeneration of rod and cone photoreceptors but no non-ocular phenotypes. The major ultrastructural feature of<jats:italic>C8orf37<\/jats:italic>KO photoreceptors was massive disorganization of the outer segment (OS) membrane discs starting from the onset of disc morphogenesis during development. At the molecular level, the amounts of multiple OS-specific membrane proteins, including proteins involved in membrane disc organization, were reduced, although these proteins were targeted normally to the OS. Considering the distribution of C8ORF37 throughout the photoreceptor cell body, the normal structure of the KO photoreceptor connecting cilium, and the absence of defects in other ciliary organs of the KO mice, our findings do not support the previous notion that C8ORF37 was a ciliary protein. Because C8ORF37 is absent in the photoreceptor OS, C8ORF37 may participate in the secretory pathway of OS membrane proteins in the photoreceptor cell body and thus maintain the homeostasis of these proteins. This study established a valid animal model for future therapeutic studies of<jats:italic>C8ORF37<\/jats:italic>-associated retinal degeneration. This study also shed new light on the role of C8ORF37 in photoreceptors and on the pathogenic mechanism underlying retinal degeneration caused by<jats:italic>C8ORF37<\/jats:italic>mutations.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>Inherited retinal degeneration is a group of incurable conditions with poorly understood underlying molecular mechanisms. We investigated<jats:italic>C8ORF37<\/jats:italic>, a causative gene for three retinal degenerative conditions: retinitis pigmentosa, cone\u2013rod dystrophy, and Bardet\u2013Biedl syndrome.<jats:italic>C8ORF37<\/jats:italic>encodes a protein with no known functional domains and thus its biological function is unpredictable. We knocked out the<jats:italic>C8ORF37<\/jats:italic>ortholog in mice, which resulted in a retinal phenotype similar to that observed in patients. We further demonstrated that C8ORF37 is required for photoreceptor outer segment disc formation and alignment, a process that is critical for photoreceptor function and survival. This study advances our understanding of the pathogenesis of retinal degeneration and establishes a valuable mouse model for future therapeutic development.<\/jats:p>","DOI":"10.1523\/jneurosci.2964-17.2018","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T17:56:39Z","timestamp":1518544599000},"page":"3160-3176","source":"Crossref","is-referenced-by-count":15,"title":["C8ORF37 Is Required for Photoreceptor Outer Segment Disc Morphogenesis by Maintaining Outer Segment Membrane Protein Homeostasis"],"prefix":"10.1523","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6540-0310","authenticated-orcid":false,"given":"Ali S.","family":"Sharif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4380-1185","authenticated-orcid":false,"given":"Dongmei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Loertscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Austin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8388-693X","authenticated-orcid":false,"given":"Kevin","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-005X","authenticated-orcid":false,"given":"Pranav D.","family":"Mathur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhuang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina S.","family":"Lobanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-3650","authenticated-orcid":false,"given":"Vadim Y.","family":"Arshavsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4799-0465","authenticated-orcid":false,"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"key":"2023041803301927000_38.13.3160.1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.116.3.659"},{"key":"2023041803301927000_38.13.3160.2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001330205"},{"key":"2023041803301927000_38.13.3160.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098939"},{"key":"2023041803301927000_38.13.3160.4","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18516"},{"key":"2023041803301927000_38.13.3160.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"2023041803301927000_38.13.3160.6","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.2.4.209"},{"key":"2023041803301927000_38.13.3160.7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh211"},{"key":"2023041803301927000_38.13.3160.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.015"},{"key":"2023041803301927000_38.13.3160.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.65.092101.142611"},{"key":"2023041803301927000_38.13.3160.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69740-7"},{"key":"2023041803301927000_38.13.3160.11","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(85)90179-4"},{"key":"2023041803301927000_38.13.3160.12","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/newbio235114a0","article-title":"Rhodopsin is the predominant protein of rod outer segment membranes","volume":"235","author":"Heitzmann","year":"1972","journal-title":"Nat New Biol"},{"key":"2023041803301927000_38.13.3160.13","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw096"},{"key":"2023041803301927000_38.13.3160.14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.495184"},{"key":"2023041803301927000_38.13.3160.15","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2501"},{"key":"2023041803301927000_38.13.3160.16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13567"},{"key":"2023041803301927000_38.13.3160.17","first-page":"68","article-title":"Novel C8orf37 mutations in patients with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia","volume":"37","author":"Katagiri","year":"2016","journal-title":"Ophthalmic Genet"},{"key":"2023041803301927000_38.13.3160.18","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2015.1066830"},{"key":"2023041803301927000_38.13.3160.19","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15647"},{"key":"2023041803301927000_38.13.3160.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.736"},{"key":"2023041803301927000_38.13.3160.21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408362200"},{"key":"2023041803301927000_38.13.3160.22","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0410"},{"key":"2023041803301927000_38.13.3160.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405160101"},{"key":"2023041803301927000_38.13.3160.24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0338-08.2008"},{"key":"2023041803301927000_38.13.3160.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232033"},{"key":"2023041803301927000_38.13.3160.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235688100"},{"key":"2023041803301927000_38.13.3160.27","doi-asserted-by":"publisher","DOI":"10.2152\/jmi.59.1"},{"key":"2023041803301927000_38.13.3160.28","first-page":"2491","article-title":"Photoreceptor membrane proteins, phototransduction, and retinal degenerative diseases. the friedenwald lecture","volume":"39","author":"Molday","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023041803301927000_38.13.3160.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.07.031"},{"key":"2023041803301927000_38.13.3160.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.03.002"},{"key":"2023041803301927000_38.13.3160.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108941200"},{"key":"2023041803301927000_38.13.3160.32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049889"},{"key":"2023041803301927000_38.13.3160.33","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2015.1071408"},{"key":"2023041803301927000_38.13.3160.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00531-1"},{"key":"2023041803301927000_38.13.3160.35","first-page":"236","article-title":"Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of pakistani origin","volume":"21","author":"Ravesh","year":"2015","journal-title":"Mol Vis"},{"key":"2023041803301927000_38.13.3160.36","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/newbio235112a0","article-title":"Molecular weight of frog rhodopsin","volume":"235","author":"Robinson","year":"1972","journal-title":"Nat New Biol"},{"key":"2023041803301927000_38.13.3160.37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm349"},{"key":"2023041803301927000_38.13.3160.38","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq319"},{"key":"2023041803301927000_38.13.3160.39","first-page":"111","article-title":"Development and degeneration of retina in rds mutant mice: observations in chimaeras of heterozygous mutant and normal genotype","volume":"98","author":"Sanyal","year":"1986","journal-title":"J Embryol Exp Morphol"},{"key":"2023041803301927000_38.13.3160.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00636-0"},{"key":"2023041803301927000_38.13.3160.41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311058200"},{"key":"2023041803301927000_38.13.3160.42","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2377"},{"key":"2023041803301927000_38.13.3160.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.10.011"},{"key":"2023041803301927000_38.13.3160.44","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-11439"},{"key":"2023041803301927000_38.13.3160.45","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr503"},{"key":"2023041803301927000_38.13.3160.46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C900853199"},{"key":"2023041803301927000_38.13.3160.47","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt764"},{"key":"2023041803301927000_38.13.3160.48","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200207153"},{"key":"2023041803301927000_38.13.3160.49","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.10.4129-4137.2005"},{"key":"2023041803301927000_38.13.3160.50","doi-asserted-by":"crossref","first-page":"5889","DOI":"10.1523\/JNEUROSCI.19-14-05889.1999","article-title":"Disruption of a retinal guanylyl cyclase gene leads to cone-specific dystrophy and paradoxical rod behavior","volume":"19","author":"Yang","year":"1999","journal-title":"J Neurosci"},{"key":"2023041803301927000_38.13.3160.51","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35891"},{"key":"2023041803301927000_38.13.3160.52","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.33.1.61"},{"key":"2023041803301927000_38.13.3160.53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2034-08.2009"},{"key":"2023041803301927000_38.13.3160.54","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37041"},{"key":"2023041803301927000_38.13.3160.55","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.042531"},{"key":"2023041803301927000_38.13.3160.56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0637349100"},{"key":"2023041803301927000_38.13.3160.57","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6141"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2964-17.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T11:17:33Z","timestamp":1681816653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.2964-17.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,13]]},"references-count":57,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2018,3,28]]},"published-print":{"date-parts":[[2018,3,28]]}},"alternative-id":["10.1523\/JNEUROSCI.2964-17.2018"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.2964-17.2018","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,13]]}}}