{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:25:44Z","timestamp":1784147144892,"version":"3.55.0"},"reference-count":60,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NEI K08 EY027463"],"award-info":[{"award-number":["NEI K08 EY027463"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005595","name":"University of California","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005595","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Retinitis pigmentosa (RP), a retinal degenerative disease, is the leading cause of heritable blindness. Previously, we described that Arap1\u2212\/\u2212 mice develop a similar pattern of photoreceptor degeneration. Arap1 is an Arf-directed GTPase-activating protein shown to modulate actin cytoskeletal dynamics. Curiously, Arap1 expression was detected in M\u00fcller glia and retinal pigment epithelium (RPE), but not the photoreceptors themselves. In this study, we generated conditional knockout mice for M\u00fcller glia\/RPE, M\u00fcller glia and RPE via targeting Rlbp1, Glast and Vmd2 promoters, respectively, to drive Cre recombinase expression to knock out Arap1. Vmd2-Cre Arap1tm1c\/tm1c and Rlbp1-Cre Arap1tm1c\/tm1c mice, but not Glast-Cre Arap1tm1c\/tm1c mice, recapitulated the phenotype originally observed in germline Arap1\u2212\/\u2212 mice. Mass spectrometry analysis of human ARAP1 co-immunoprecipitation identified candidate binding partners of ARAP1, revealing potential interactants involved in phagocytosis, cytoskeletal composition, intracellular trafficking and endocytosis. Quantification of outer segment phagocytosis in vivo demonstrated a clear phagocytic defect in Arap1\u2212\/\u2212 mice compared to Arap1+\/+ controls. We conclude that Arap1 expression in RPE is necessary for photoreceptor survival due to its indispensable function in RPE phagocytosis.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.049343","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T08:49:28Z","timestamp":1656319768000},"source":"Crossref","is-referenced-by-count":7,"title":["<i>Arap1<\/i> loss causes retinal pigment epithelium phagocytic dysfunction and subsequent photoreceptor death"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1647-5073","authenticated-orcid":false,"given":"Andy","family":"Shao","sequence":"first","affiliation":[{"name":"The University of Nevada, Reno School of Medicine 1 , Reno, NV 89557 , USA"},{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jacobo","family":"Lopez","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiaJia","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Addy","family":"Tham","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seanne","family":"Javier","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Quiroz","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Frick","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-2805","authenticated-orcid":false,"given":"Edward M.","family":"Levine","sequence":"additional","affiliation":[{"name":"Vanderbilt University 3 Department of Ophthalmology and Visual Sciences , , Nashville, TN 37235 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. C. Kent","family":"Lloyd","sequence":"additional","affiliation":[{"name":"UC Davis 4 Mouse Biology Program , , Davis, CA 95616 , USA"},{"name":"School of Medicine, UC Davis 5 Department of Surgery , , Sacramento, CA 95817 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Leonard","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, UC Davis 6 Department of Surgical and Radiological Sciences , , Davis, CA 95616 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Murphy","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"},{"name":"School of Veterinary Medicine, UC Davis 6 Department of Surgical and Radiological Sciences , , Davis, CA 95616 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Glaser","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis 7 Department of Cell Biology and Human Anatomy , , Davis, CA 95616 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-8094","authenticated-orcid":false,"given":"Ala","family":"Moshiri","sequence":"additional","affiliation":[{"name":"School of Medicine, UC Davis, Sacramento, CA 95817 2 Department of Ophthalmology and Vision Science , , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"2022072508325675500_DMM049343C1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.exer.2014.01.015","article-title":"Cultured primary human fetal retinal pigment epithelium (hfRPE) as a model for evaluating RPE metabolism","volume":"126","author":"Adijanto","year":"2014","journal-title":"Exp. 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