{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:09:36Z","timestamp":1790932176166,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft\u0131rma Kurumu","doi-asserted-by":"publisher","award":["219S943"],"award-info":[{"award-number":["219S943"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>carbohydrate sulfotransferase 6<\/jats:italic>\n                    (\n                    <jats:italic>chst6<\/jats:italic>\n                    ) gene is linked to macular corneal dystrophy (MCD), a rare disease that leads to bilateral blindness due to the accumulation of opaque aggregates in the corneal stroma.\n                    <jats:italic>chst6<\/jats:italic>\n                    encodes for a keratan sulfate proteoglycan (KSPG) specific sulfotransferase. MCD patients lose sulfated KSPGs (cKS) in the cornea and the serum. The significance of serum cKS loss has not been understood. Zebrafish cornea structure is similar to that of humans and it contains high levels of sulfated cKS in the stroma. Here, zebrafish\n                    <jats:italic>chst6<\/jats:italic>\n                    is shown to be expressed in the cornea and head structures of the embryos. An animal model of MCD is developed by generating\n                    <jats:italic>chst6<\/jats:italic>\n                    mutant animals with CRISPR\/Cas9\u2010mediated gene editing. The dramatic decrease in cKS epitopes in the mutants was shown with ELISA and immunofluorescence. Morphological defects or alterations of jaw cartilage were detected in a minor fraction of the mutant larvae. Loss of cKS epitopes and morphological defects was fully rescued with wild\u2010type\n                    <jats:italic>chst6<\/jats:italic>\n                    . Mutant adult zebrafish displayed all clinical manifestations of MCD, while a fraction also displayed jaw and skeleton defects. Opaque accumulations formed in the eye, which were alcian blue positive. Loss of cKS in the corneal stroma and a decrease in corneal thickness were shown. Interestingly, alteration of transforming growth factor beta\u2010induced (BIGH3) expression which was not described in patients was also observed. This is the first report of an MCD model in a genetically tractable organism, providing a preclinical model and insight into the importance of KSPG sulfation for proper skeletal morphogenesis.\n                  <\/jats:p>","DOI":"10.1111\/febs.17337","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T13:04:41Z","timestamp":1733490281000},"page":"373-390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Loss of\n                    <i>carbohydrate sulfotransferase 6<\/i>\n                    function leads to macular corneal dystrophy phenotypes and skeletal defects in zebrafish"],"prefix":"10.1111","volume":"292","author":[{"given":"Merve","family":"Basol","sequence":"first","affiliation":[{"name":"Izmir Biomedicine and Genome Center  Turkey"},{"name":"Izmir International Biomedicine and Genome Institute Dokuz Eyl\u00fcl University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Ersoz\u2010Gulseven","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helin","family":"Ozaktas","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center  Turkey"},{"name":"Izmir International Biomedicine and Genome Institute Dokuz Eyl\u00fcl University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-0757","authenticated-orcid":false,"given":"Sibel","family":"Kalyoncu","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canan Asli","family":"Utine","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center  Turkey"},{"name":"Department of Ophthalmology, Faculty of Medicine Dokuz Eylul University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-5979","authenticated-orcid":false,"given":"Gulcin","family":"Cakan\u2010Akdogan","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center  Turkey"},{"name":"Department of Medical Biology, Faculty of Medicine Dokuz Eyl\u00fcl University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.06.021"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927615000483"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2009.11.013"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/glycobiology.3e.017"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwy003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/75664"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0740"},{"key":"e_1_2_10_9_1","first-page":"167","article-title":"Macular corneal dystrophy","volume":"89","author":"Klintworth GK","year":"1977","journal-title":"Am J Pathol"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540214932"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2008.139527"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103227200"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780281209"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-9120(92)90263-R"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(90)32436-3"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713681003760150"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medidd.2021.100095"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2016.102"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605441103"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1611"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2017.1385087"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-007-9046-z"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707656200"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.043679"},{"key":"e_1_2_10_25_1","unstructured":"ThisseB&ThisseC(2004)Fast Release Clones: A High Throughput Expression Analysis. 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