{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:59:42Z","timestamp":1780574382944,"version":"3.54.1"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273019"],"award-info":[{"award-number":["32273019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2025,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Urate transporter 1 (URAT1) is a well\u2010known therapeutic target for reducing urate levels in the treatment of hyperuricemia and gout. However, current pharmacological studies have failed to evaluate the efficacy of URAT1 inhibitors in non\u2010primate animal models. We established a\n human URAT1<\/jats:italic>\n (\n hURAT1<\/jats:italic>\n ) transgenic knock\u2010in (KI) mouse model to assess uricosuric agents' effectiveness and characterize URAT1\u2010caused pathogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We generated\n hURAT1<\/jats:italic>\n transgenic mice using CRISPR\/Cas9 KI technique.\n mUrat1<\/jats:italic>\n knockout was achieved by replacing exon 1 coding sequence with a human\n SLC22A12<\/jats:italic>\n coding sequence (CDS)\u2010pA cassette. Based on the above transgenic mice, a hyperuricemia model was further established by hypoxanthine administration.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n hURAT1<\/jats:italic>\n \u2010KI mice successfully expressed hURAT1 protein to the apical side of the kidney proximal tubule epithelium, where native human URAT1 is localized in human kidney. Upon hypoxanthine challenge, the blood uric acid (UA) level was elevated in\n hURAT1\u2010<\/jats:italic>\n KI mice (251\u2009\u03bcmol\/L), showing an approximately 37% increase compared to wild\u2010type (WT) mice (183.5\u2009\u03bcmol\/L). The elevated blood UA level could be alleviated by hURAT1 inhibitor benzbromarone treatment in the\n hURAT1<\/jats:italic>\n \u2010KI mice (164.2\u2009\u03bcmol\/L vs. 251\u2009\u03bcmol\/L,\n p<\/jats:italic>\n \u2009<\u20090.05) whereas no response was observed in\n WT<\/jats:italic>\n littermates (168.8\u2009\u03bcmol\/L vs. 183.5\u2009\u03bcmol\/L).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The\n hURAT1<\/jats:italic>\n \u2010KI hyperuricemia mouse model would be valuable for preclinical evaluation of gout treatment with urate\u2010lowering drugs and for studying UA metabolic complexities in humans.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/1756-185x.70034","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T23:09:54Z","timestamp":1735600194000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["\n hURAT1<\/i>\n <\/scp>\n Transgenic Mouse Model for Evaluating Targeted Urate\u2010Lowering Agents"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3772-1819","authenticated-orcid":false,"given":"Weiyan","family":"Cai","sequence":"first","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4444-2113","authenticated-orcid":false,"given":"Miyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Medicine The University of Texas at Tyler School of Medicine Tyler Texas USA"},{"name":"Center for Biomedical Research The University of Texas Health Science Center at Tyler Tyler Texas USA"},{"name":"Department of Cellular and Molecular Biology The University of Texas Health Science Center at Tyler Tyler Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihui","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1936-2007","authenticated-orcid":false,"given":"Apeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Children\u2019s Hospital of Nanjing MedicalUniversity Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-5052","authenticated-orcid":false,"given":"Gejing","family":"De","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing 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