{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:50:22Z","timestamp":1778511022921,"version":"3.51.4"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R21GM114645"],"award-info":[{"award-number":["R21GM114645"]}]},{"name":"National Institutes of Health","award":["R01HD090180"],"award-info":[{"award-number":["R01HD090180"]}]},{"name":"National Institutes of Health","award":["R01DC019735"],"award-info":[{"award-number":["R01DC019735"]}]},{"name":"National Institutes of Health","award":["R01HD109750"],"award-info":[{"award-number":["R01HD109750"]}]},{"name":"National Institutes of Health","award":["R01EY020545"],"award-info":[{"award-number":["R01EY020545"]}]},{"name":"National Institutes of Health","award":["R01EY029705"],"award-info":[{"award-number":["R01EY029705"]}]},{"name":"National Institutes of Health","award":["1R50CA283805-01A1"],"award-info":[{"award-number":["1R50CA283805-01A1"]}]},{"name":"National Institutes of Health","award":["P30CA016056"],"award-info":[{"award-number":["P30CA016056"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["R21GM114645"],"award-info":[{"award-number":["R21GM114645"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["R01HD090180"],"award-info":[{"award-number":["R01HD090180"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["R01DC019735"],"award-info":[{"award-number":["R01DC019735"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["R01HD109750"],"award-info":[{"award-number":["R01HD109750"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["R01EY020545"],"award-info":[{"award-number":["R01EY020545"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["R01EY029705"],"award-info":[{"award-number":["R01EY029705"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["1R50CA283805-01A1"],"award-info":[{"award-number":["1R50CA283805-01A1"]}]},{"name":"National Institutes of Health to Roswell Park Comprehensive Cancer Center","award":["P30CA016056"],"award-info":[{"award-number":["P30CA016056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Choroideremia is a rare X-linked recessive retinal disorder characterized by progressive vision loss caused by retinal degeneration resulting from mutations in the CHM gene, which encodes Rab escort protein 1 (REP-1). In humans and mice, the Rab escort protein (REP) family consists of two members, REP-1 and REP-2, with REP-2 hypothesized to compensate for REP-1 deficiency in tissues outside the eye in choroideremia. In this study, we conducted a systematic mutational analysis of the mouse orthologs of REP-1 and REP-2. Blood analyses revealed metabolic abnormalities in the mutant mice deficient for REP-1, resembling the systemic metabolic disturbances observed in individuals with choroideremia, such as altered lipid and hemoglobin metabolism. We also observed an elevation in systemic inflammatory biomarkers in these mutant mice. Interestingly, these systemic abnormalities emerged before retinal degeneration became detectable in REP-1-deficient mice. Transcriptomic analysis of retinas isolated from REP-1 deficient mice revealed enrichment of proinflammatory signaling pathways. These results suggest important similarities between choroideremia and some forms of retinitis pigmentosa. While engineered loss of REP-2 alone caused no detectable phenotypic changes, dual deficiency in REP-1 and REP-2 resulted in lethality under both in vivo and in vitro conditions. Our findings offer novel insights into REPs and deepen our understanding of choroideremia, which may contribute to the development of new treatments for this genetic condition.<\/jats:p>","DOI":"10.3390\/ijms26083636","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T06:18:36Z","timestamp":1744611516000},"page":"3636","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Analysis of Choroideremia-Related Rab Escort Proteins"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-6630","authenticated-orcid":false,"given":"Zhuo","family":"Xing","sequence":"first","affiliation":[{"name":"The Children\u2019s Guild Foundation Down Syndrome Research Program, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuguo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ross Eye Institute, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0966-6488","authenticated-orcid":false,"given":"Eduardo","family":"Cortes-Gomez","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Pao","sequence":"additional","affiliation":[{"name":"The Children\u2019s Guild Foundation Down Syndrome Research Program, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingqiu","family":"Gao","sequence":"additional","affiliation":[{"name":"The Children\u2019s Guild Foundation Down Syndrome Research Program, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3203-8112","authenticated-orcid":false,"given":"Avrium","family":"Douglas","sequence":"additional","affiliation":[{"name":"The Children\u2019s Guild Foundation Down Syndrome Research Program, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichen","family":"Li","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5049-4737","authenticated-orcid":false,"given":"Joseph A.","family":"Spernyak","sequence":"additional","affiliation":[{"name":"Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5286-6506","authenticated-orcid":false,"given":"G. William","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prashant K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-0409","authenticated-orcid":false,"given":"Jianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4802-4952","authenticated-orcid":false,"given":"Yasmin","family":"Thanavala","sequence":"additional","affiliation":[{"name":"Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian M.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8003-7529","authenticated-orcid":false,"given":"Xiuqian","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ross Eye Institute, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y. Eugene","family":"Yu","sequence":"additional","affiliation":[{"name":"The Children\u2019s Guild Foundation Down Syndrome Research Program, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"},{"name":"Genetics, Genomics and Bioinformatics Program, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). Choroideremia. GeneReviews((R)), University of Washington."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1097\/ICU.0000000000000392","article-title":"Choroideremia","volume":"28","author":"Dimopoulos","year":"2017","journal-title":"Curr. Opin. 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