{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:20:20Z","timestamp":1760235620076,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201508500109"],"award-info":[{"award-number":["201508500109"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C14\/17\/113"],"award-info":[{"award-number":["C14\/17\/113"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["12I3820N"],"award-info":[{"award-number":["12I3820N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystinosis is a rare, incurable, autosomal recessive disease caused by mutations in the CTNS gene. This gene encodes the lysosomal cystine transporter cystinosin, leading to lysosomal cystine accumulation in all cells of the body, with kidneys being the first affected organs. The current treatment with cysteamine decreases cystine accumulation, but does not reverse the proximal tubular dysfunction, glomerular injury or loss of renal function. In our previous study, we have developed a zebrafish model of cystinosis through a nonsense mutation in the CTNS gene and have shown that zebrafish larvae recapitulate the kidney phenotype described in humans. In the current study, we characterized the adult cystinosis zebrafish model and evaluated the long-term effects of the disease on kidney and extra renal organs through biochemical, histological, fertility and locomotor activity studies. We found that the adult cystinosis zebrafish presents cystine accumulation in various organs, altered kidney morphology, impaired skin pigmentation, decreased fertility, altered locomotor activity and ocular anomalies. Overall, our data indicate that the adult cystinosis zebrafish model reproduces several human phenotypes of cystinosis and may be useful for studying pathophysiology and long-term effects of novel therapies.<\/jats:p>","DOI":"10.3390\/ijms22179398","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:01:37Z","timestamp":1630321297000},"page":"9398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Renal and Extra Renal Manifestations in Adult Zebrafish Model of Cystinosis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-7360","authenticated-orcid":false,"given":"Sante Princiero","family":"Berlingerio","sequence":"first","affiliation":[{"name":"Laboratory of Pediatric Nephrology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junling","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3329-3474","authenticated-orcid":false,"given":"Lies","family":"De Groef","sequence":"additional","affiliation":[{"name":"Neural Circuit Development and Regeneration Research Group, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold","family":"Taeter","sequence":"additional","affiliation":[{"name":"Group of M3-BIORES, Division of Animal and Human Health Engineering, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0161-3189","authenticated-orcid":false,"given":"Tomas","family":"Norton","sequence":"additional","affiliation":[{"name":"Group of M3-BIORES, Division of Animal and Human Health Engineering, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-581X","authenticated-orcid":false,"given":"Pieter","family":"Baatsen","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology, VIB-KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-0974","authenticated-orcid":false,"given":"Sara","family":"Cairoli","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine, Laboratory of Metabolic Biochemistry Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Goffredo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Medicine, Laboratory of Metabolic Biochemistry Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9989-9567","authenticated-orcid":false,"given":"Peter","family":"de Witte","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Biodiscovery, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lambertus","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Pediatric Nephrology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1214-500X","authenticated-orcid":false,"given":"Hans J.","family":"Baelde","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-7312","authenticated-orcid":false,"given":"Elena","family":"Levtchenko","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13023-016-0426-y","article-title":"Cystinosis: A review","volume":"11","author":"Elmonem","year":"2016","journal-title":"Orphanet J. 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