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Mutations in its encoding gene\n                    <jats:italic>RLBP1<\/jats:italic>\n                    lead to inherited retinal diseases with the common feature of poor night vision. Zebrafish possess two\n                    <jats:italic>RLBP1<\/jats:italic>\n                    paralogs,\n                    <jats:italic>rlbp1a<\/jats:italic>\n                    and\n                    <jats:italic>rlbp1b,<\/jats:italic>\n                    with distinct retinal expression profiles, providing a bespoke opportunity to dissect cell\u2010specific functions of CRALBP. Here, we first resolved conflicting reports on paralog expression by interrogating zebrafish single\u2010cell RNA\u2010sequencing datasets, which revealed predominant\n                    <jats:italic>rlbp1a<\/jats:italic>\n                    expression in M\u00fcller glia and\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    expression in the RPE. Using CRISPR\u2010generated zebrafish knockouts, we demonstrated that loss of RPE\u2010expressed\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    selectively impaired optokinetic responses (OKR) with a ~50% reduction in saccade frequency relative to wildtype. This impaired OKR response is only seen when under dim light conditions with no defect seen in standard or bright light rearing conditions. This recapitulates the night blindness presentation in patients with\n                    <jats:italic>RLBP1<\/jats:italic>\n                    mutations. Retinoid profiling of\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    knockout larvae showed significant decreases in 11\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010retinal (62% reduced) and all\u2010\n                    <jats:italic>trans<\/jats:italic>\n                    \u2010retinal (69% reduced) levels. To explore mechanistic changes following\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    loss, unbiased proteomic profiling was carried out on\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    knockout adult zebrafish eyes. This confirmed the knockout of Cralbpb and revealed significant disruption of proteins involved in vitamin A metabolism, lipid metabolism\/storage and ferroptosis. To explore the utility of zebrafish for in\u00a0vivo pathogenicity assessment of\n                    <jats:italic>RLBP1<\/jats:italic>\n                    , we established a complementation assay using transgenic zebrafish. Although expression of wildtype EGFP\u2010tagged human\n                    <jats:italic>RLBP1<\/jats:italic>\n                    did not rescue the visual deficit, expression of zebrafish Cralbp to the RPE restored dim light vision, whereas zebrafish Cralbp harboring the human pathogenic p.R151Q mutation failed to do so. Together, these findings underscore the predominant role of RPE\u2010expressed CRALBP in sustaining visual function under low\u2010light conditions and establish a zebrafish platform for functional evaluation of\n                    <jats:italic>RLBP1<\/jats:italic>\n                    variants.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500600r","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T03:28:36Z","timestamp":1750908516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Germline Disruption of Retinal Pigment Epithelium\u2010Expressed Zebrafish\n                    <i>rlbp1b<\/i>\n                    <sup>\u2212\/\u2212<\/sup>\n                    Results in Selective Dim Light Visual Behavior Deficits and Provides a Screening Platform for Evaluating the Pathogenicity of Human\n                    <scp>\n                      <i>RLBP1<\/i>\n                    <\/scp>\n                    Variants"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-4236","authenticated-orcid":false,"given":"John D.","family":"Fehilly","sequence":"first","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2206-6221","authenticated-orcid":false,"given":"Tess","family":"McCann","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin  Dublin 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Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-8642","authenticated-orcid":false,"given":"Rebecca","family":"Ward","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"},{"name":"UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieran","family":"Wynne","sequence":"additional","affiliation":[{"name":"Systems Biology Ireland University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia G\u00f3mez","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin  Dublin 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