{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:43:56Z","timestamp":1787028236044,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["21\/310"],"award-info":[{"award-number":["21\/310"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Gout is caused by elevated serum urate leading to the deposition of monosodium urate (MSU) crystals that can trigger episodes of acute inflammation. Humans are sensitive to developing gout because they lack a functional urate-metabolizing enzyme called uricase\/urate oxidase (encoded by the UOX gene). A hallmark of long-standing disease is tophaceous gout, characterized by the formation of tissue-damaging granuloma-like structures (\u2018tophi\u2019) composed of densely packed MSU crystals and immune cells. Little is known about how tophi form, largely due to the lack of suitable animal models in which the host response to MSU crystals can be studied in vivo long-term. We have previously described a larval zebrafish model of acute gouty inflammation where the host response to microinjected MSU crystals can be live imaged within an intact animal. Although useful for modeling acute inflammation, crystals are rapidly cleared following a robust innate immune response, precluding analysis at later stages. Here we describe a zebrafish uox null mutant that possesses elevated urate levels at larval stages. Uricase-deficient \u2018hyperuricemic\u2019 larvae exhibit a suppressed acute inflammatory response to MSU crystals and prolonged in vivo crystal persistence. Imaging of crystals at later stages reveals that they form granuloma-like structures dominated by macrophages. We believe that uox\u2212\/\u2212 larvae will provide a useful tool to explore the transition from acute gouty inflammation to tophus formation, one of the remaining mysteries of gout pathogenesis.<\/jats:p>","DOI":"10.3390\/genes13122179","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T08:27:29Z","timestamp":1669105649000},"page":"2179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Uricase-Deficient Larval Zebrafish with Elevated Urate Levels Demonstrate Suppressed Acute Inflammatory Response to Monosodium Urate Crystals and Prolonged Crystal Persistence"],"prefix":"10.3390","volume":"13","author":[{"given":"Tanja","family":"Linnerz","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-4377","authenticated-orcid":false,"given":"Yih Jian","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Rolland","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3554-0133","authenticated-orcid":false,"given":"Jonathan W.","family":"Astin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Dalbeth","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1093\/rheumatology\/kez476","article-title":"Global, regional and national burden of gout, 1990\u20132017: A systematic analysis of the Global Burden of Disease Study","volume":"59","author":"Xia","year":"2020","journal-title":"Rheumatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/icb.2009.89","article-title":"Innate inflammation and resolution in acute gout","volume":"88","author":"Martin","year":"2010","journal-title":"Immunol. 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