{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:26:26Z","timestamp":1792797986938,"version":"4.5.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,9,21]]},"abstract":"<jats:p>\n                    With the notable exception of humans, uric acid is degraded to (S)-allantoin in a biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU) hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase in most vertebrate species. A point mutation in the gene encoding mouse HIU hydrolase,\n                    <jats:italic>Urah<\/jats:italic>\n                    , that perturbed uric acid metabolism within the liver was discovered during a mutagenesis screen in mice. The predicted substitution of cysteine for tyrosine in a conserved helical region of the mutant-encoded HIU hydrolase resulted in undetectable protein expression. Mice homozygous for this mutation developed elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also developed hepatocellular carcinoma, and tumor development was accelerated by exposure to radiation. The development of hepatomegaly and liver tumors in mice lacking\n                    <jats:italic>Urah<\/jats:italic>\n                    suggests that uric acid metabolites may be toxic and that urate oxidase activity without HIU hydrolase function may affect liver growth and transformation. The absence of HIU hydrolase in humans predicts slowed metabolism of HIU after clinical administration of exogenous urate oxidase in conditions of uric acid-related pathology. The data suggest that prolonged urate oxidase therapy should be combined with careful assessment of toxicity associated with extrahepatic production of uric acid metabolites.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1010390107","type":"journal-article","created":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T22:21:32Z","timestamp":1283898092000},"page":"16625-16630","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["Deficiency of 5-hydroxyisourate hydrolase causes hepatomegaly and hepatocellular carcinoma in mice"],"prefix":"10.1073","volume":"107","author":[{"given":"William S.","family":"Stevenson","sequence":"first","affiliation":[{"name":"Department of Haematology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales 2065, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig D.","family":"Hyland","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Guo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip O.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Willson","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales 2065, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne A.","family":"Hilton","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Viney","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Bahlo","sequence":"additional","affiliation":[{"name":"Bioinformatics Division, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth L.","family":"Masters","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hennebry","sequence":"additional","affiliation":[{"name":"Baker International Diabetes Institute, Heart and Diabetes Institute, Melbourne 3004, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Richardson","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Royal Melbourne Institute of Technology University, Bundoora 3083, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicos A.","family":"Nicola","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Metcalf","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Hilton","sequence":"additional","affiliation":[{"name":"Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren S.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Division,"},{"name":"Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,9,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio768"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio0306-124"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.23.9412"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.1.144"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.36.6.1072"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.6858"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000028589.66335.AA"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg112"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03408.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07246.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1016-8478(23)17402-4","article-title":"Mouse transthyretin-related protein is a hydrolase which degrades 5-hydroxyisourate, the end product of the uricase reaction","volume":"22","author":"Lee Y","year":"2006","unstructured":"Y Lee, et al., Mouse transthyretin-related protein is a hydrolase which degrades 5-hydroxyisourate, the end product of the uricase reaction. Mol Cells 22, 141\u2013145 (2006).","journal-title":"Mol Cells"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04889.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.04.057"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600523103"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.07.079"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.6.2162.bloodjournal8762162"},{"key":"e_1_3_3_17_2","first-page":"159","volume-title":"Pathology and Genetics of Tumours of the Digestive System","author":"Hirohashi S","year":"2000","unstructured":"S Hirohashi, K Ishak, M Kojiro, Hepatocellular carcinoma. Pathology and Genetics of Tumours of the Digestive System, eds S Hamilton, L Aaltonen (International Agency for Research on Cancer, Lyon, France), pp. 159\u2013172 (2000)."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.23.9081"},{"key":"e_1_3_3_19_2","first-page":"100","article-title":"Tissue specificity and species differences in the distribution of urate oxidase in peroxisomes","volume":"58","author":"Usuda N","year":"1988","unstructured":"N Usuda, MK Reddy, T Hashimoto, MS Rao, JK Reddy, Tissue specificity and species differences in the distribution of urate oxidase in peroxisomes. Lab Invest 58, 100\u2013111 (1988).","journal-title":"Lab Invest"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.5530140711"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1999.00452.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035363"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23993"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1200\/JCO.2003.04.115","article-title":"Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: Results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study","volume":"21","author":"Coiffier B","year":"2003","unstructured":"B Coiffier, et al., Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: Results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study. J Clin Oncol 21, 4402\u20134406 (2003).","journal-title":"J Clin Oncol"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.2998"},{"key":"e_1_3_3_26_2","first-page":"2093","article-title":"Rasburicase for tophaceous gout not treatable with allopurinol: An exploratory study","volume":"34","author":"Richette P","year":"2007","unstructured":"P Richette, C Bri\u00e8re, V Hoenen-Clavert, D Loeuille, T Bardin, Rasburicase for tophaceous gout not treatable with allopurinol: An exploratory study. J Rheumatol 34, 2093\u20132098 (2007).","journal-title":"J Rheumatol"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23810"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22403"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.106.480699"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.09.011"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008317589"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/108.2.457"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/131.2.423"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.17.5322"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1010390107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T02:41:22Z","timestamp":1711766482000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1010390107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,7]]},"references-count":34,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2010,9,21]]}},"alternative-id":["10.1073\/pnas.1010390107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1010390107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,7]]},"assertion":[{"value":"2010-09-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}