{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:29:39Z","timestamp":1788881379756,"version":"build-2803163510"},"reference-count":61,"publisher":"The Company of Biologists","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100013647","name":"College of Natural Sciences, University of Massachusetts Amherst","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013647","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["1951420"],"award-info":[{"award-number":["1951420"]}]},{"name":"Foundation Fighting Blindness","award":["BR-CMM-0622-0835-UMASS"],"award-info":[{"award-number":["BR-CMM-0622-0835-UMASS"]}]},{"DOI":"10.13039\/100008975","name":"University of Massachusetts Amherst","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008975","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Stargardt disease (STGD), the leading cause of inherited childhood blindness, is primarily caused by mutations in the ABCA4 gene; yet, the underlying mechanisms of photoreceptor degeneration remain elusive, partly due to limitations in existing animal disease models. To expand our understanding, we mutated the human ABCA4 paralogues abca4a and abca4b in zebrafish, which has a cone-rich retina. Our study unveiled striking dysmorphology and elongation of cone outer segments (COS) in abca4a;abca4b double mutants, alongside reduced phagocytosis by the retinal pigmented epithelium (RPE). We report that zebrafish Abca4 protein forms a distinctive stripe along the length of COS, suggesting a potential structural role. We further show that, in wild-type zebrafish, outer segments of cone cells constitutively present externalized phosphatidylserine, an apoptotic \u2018eat-me\u2019 signal, and that this pattern is disrupted in abca4a;abca4b double mutants, potentially contributing to reduced RPE phagocytic activity. More broadly, constitutive presentation of the \u2018eat-me\u2019 signal by COS \u2212 if conserved in humans \u2013 might have important implications for other retinal degenerative diseases, including age-related macular degeneration. Our zebrafish model provides novel insights into cone dysfunction and presents a promising platform for unraveling the mechanisms of STGD pathogenesis and advancing therapeutic interventions.<\/jats:p>","DOI":"10.1242\/dmm.052052","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T08:46:27Z","timestamp":1732869987000},"source":"Crossref","is-referenced-by-count":9,"title":["Abca4, mutated in Stargardt disease, is required for structural integrity of cone outer segments"],"prefix":"10.1242","volume":"18","author":[{"given":"John J.","family":"Willoughby","sequence":"first","affiliation":[{"name":"University of Massachusetts Biology Department , , Amherst, MA 01003 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-4031","authenticated-orcid":false,"given":"Abbie M.","family":"Jensen","sequence":"additional","affiliation":[{"name":"University of Massachusetts Biology Department , , Amherst, MA 01003 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"2025011010432159600_DMM052052C1","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/ng0397-236","article-title":"A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy","volume":"15","author":"Allikmets","year":"1997","journal-title":"Nat. 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