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We used CRISPR\/Cas9 to induce prom1-null mutations in Xenopus laevis and then tracked retinal disease progression from the ages of 6\u2005weeks to 3\u2005years. We found that prom1-null-associated retinal degeneration in frogs was age-dependent and involved retinal pigment epithelium (RPE) dysfunction preceding photoreceptor degeneration. Before photoreceptor degeneration occurred, aging prom1-null frogs developed larger and increasing numbers of cellular debris deposits in the subretinal space and outer segment layer, which resembled subretinal drusenoid deposits (SDDs) in their location, histology and representation as seen by color fundus photography and optical coherence tomography (OCT). Evidence for an RPE origin of these deposits included infiltration of pigment granules into the deposits, thinning of the RPE as measured by OCT, and RPE disorganization as measured by histology and OCT. The appearance and accumulation of SDD-like deposits and RPE thinning and disorganization in our animal model suggests an underlying disease mechanism for prom1-null-mediated blindness that involves death and dysfunction of the RPE preceding photoreceptor degeneration, instead of direct effects upon photoreceptor outer segment morphogenesis, as was previously hypothesized.<\/jats:p>","DOI":"10.1242\/jcs.262298","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T04:31:35Z","timestamp":1727843495000},"source":"Crossref","is-referenced-by-count":6,"title":["<i>prominin-1<\/i>\n                    -null\n                    <i>Xenopus laevis<\/i>\n                    develop subretinal drusenoid-like deposits, cone-rod dystrophy and RPE atrophy"],"prefix":"10.1242","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-1243","authenticated-orcid":false,"given":"Brittany J.","family":"Carr","sequence":"first","affiliation":[{"name":"The University of Alberta 1 , Faculty of Medicine and Dentistry, Department of Ophthalmology and Visual Sciences , Edmonton, AB T6G 2E1 ,","place":["Canada"]},{"name":"The University of Alberta 2 , Faculty of Medicine and Dentistry, Department of Cell Biology, Edmonton, AB T6G 2H7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Skitsko","sequence":"additional","affiliation":[{"name":"The University of British Columbia 3 , Faculty of Medicine, Department of Ophthalmology and Visual Sciences, Vancouver, BC V5Z 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linnea M.","family":"Kriese","sequence":"additional","affiliation":[{"name":"The University of Alberta 1 , Faculty of Medicine and Dentistry, Department of Ophthalmology and Visual Sciences , Edmonton, AB T6G 2E1 ,","place":["Canada"]},{"name":"The University of Alberta 2 , Faculty of Medicine and Dentistry, Department of Cell Biology, Edmonton, AB T6G 2H7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Song","sequence":"additional","affiliation":[{"name":"The University of British Columbia 4 , Faculty of Applied Science, Faculty of Medicine, School of Biomedical Engineering, Vancouver, BC V6T 2B9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Li","sequence":"additional","affiliation":[{"name":"The University of Alberta 1 , Faculty of Medicine and Dentistry, Department of Ophthalmology and Visual Sciences , Edmonton, AB T6G 2E1 ,","place":["Canada"]},{"name":"The University of Alberta 2 , Faculty of Medicine and Dentistry, Department of Cell Biology, Edmonton, AB T6G 2H7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4907-3732","authenticated-orcid":false,"given":"Myeong Jin","family":"Ju","sequence":"additional","affiliation":[{"name":"The University of British Columbia 3 , Faculty of Medicine, Department of Ophthalmology and Visual Sciences, Vancouver, BC V5Z 0A6 ,","place":["Canada"]},{"name":"The University of British Columbia 4 , Faculty of Applied Science, Faculty of Medicine, School of Biomedical Engineering, Vancouver, BC V6T 2B9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6183-6499","authenticated-orcid":false,"given":"Orson L.","family":"Moritz","sequence":"additional","affiliation":[{"name":"The University of British Columbia 3 , Faculty of Medicine, Department of Ophthalmology and Visual Sciences, Vancouver, BC V5Z 0A6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"2024111208385732300_JCS262298C1","first-page":"117","article-title":"Mammalian cones: disc shedding phagocytosis, and renewal","volume":"17","author":"Anderson","year":"1978","journal-title":"Invest. 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