Elucidation of environmental factors involved in the onset of hyperuricemia using complete model animals of human uric acid metabolism

• Project/Area Number: 26460347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Teikyo University
• Principal Investigator: Hosoyamada Makoto 帝京大学, 薬学部, 教授 (00291659)
• Co-Investigator(Kenkyū-buntansha): 富岡 直子 帝京大学, 薬学部, 助教 (60525814) ; 金子 希代子 帝京大学, 薬学部, 教授 (90147075) ; 関根 祐子 千葉大学, 大学院薬学研究院, 教授 (30567350)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 尿酸

Outline of Final Research Achievements

1. Successful breeding of B6/XcMSM mice reported to have a higher HPRT activity than experimental mice such as C57BL/6 and successive breeding exceeding reproductive septa associated with subspecies differences. 2. We confirmed that B6/XcMSM mice have HPRT high activity allele and established genotyping method of HPRT allele. 3. By using B6/XcMSM mouse, suppression of hypoxanthine release by blood purinergic system with HPRT high activity was observed in blood cells without Xanthine oxidoreductase (Xor) activity. 4. UoxKO-XcMSM mouse creation enabled us to obtain mice that were close to human uric acid metabolism except that Xor was highly active.

Research Products

• [Journal Article] Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury (2016)
  • Author(s): Hosoyamada M, Tsurumi Y, Hirano H, Tomioka NH, Sekine Y, Morisaki T, Uchida S.
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. Volume: 35 Issue: 10-12 Pages: 543
  • DOI: 10.1080/15257770.2016.1143559
  • URL: https://localhost/en/publications/7877323a-6d37-4582-a545-addad4e64f5c
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The mechanism of false in vitro elevation of uric acid level in mouse blood. (2016)
  • Author(s): Watanabe T, Tomioka NH, Watanabe S, Suzuki Y, Tsuchiya M, Hosoyamada M
  • Journal Title: Biol. Pharm. Bull.
  • NAID: 130005160780
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Apoptosis induced by an uromodulin mutant C112Y and its suppression by topiroxostat (2014)
  • Author(s): Utami SB, Mahati E, Li P, Maharani N, Ikeda N, Bahrudin U, Munemura C, Hosoyamada M, Yamamoto Y, Yoshida A, Nakayama Y, Higaki K, Nanba E, Ninomiya H, Shirayoshi Y, Ichida K, Yamamoto K, Hosoya T, Hisatome I.
  • Journal Title: Clin Exp Nephrol. 2014 Sep 20. Volume: 19 Issue: 4 Pages: 576
  • DOI: 10.1007/s10157-014-1032-8
  • URL: https://localhost/en/publications/e05f12ff-96a0-411c-92e1-565a5cde650f
  • Peer Reviewed
• [Journal Article] Identification of a hypouricemia patient with SLC2A9 R380W, a pathogenic mutation for renal hypouricemia type 2. (2014)
  • Author(s): Chiba T, Matsuo H, Nagamori S, Nakayama A, Kawamura Y, Shimizu S, Sakiyama M, Hosoyamada M, Kawai S, Okada R, Hamajima N, Kanai Y, Shinomiya N.
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. Volume: 33 Issue: 4-6 Pages: 261-5
  • DOI: 10.1080/15257770.2013.857781
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] False in vitro and in vivo elevations of uric acid levels in mouse blood (2014)
  • Author(s): Watanabe T, Tomioka NH, Watanabe S, Tsuchiya M, Hosoyamada M.
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. Volume: 33 Issue: 4-6 Pages: 192
  • DOI: 10.1080/15257770.2013.865742
  • URL: https://pure.teikyo.jp/en/publications/d86ae868-f2db-443b-ae80-adb7105c9111
  • Peer Reviewed
• [Presentation] HPRT高活性マウスを用いた血漿尿酸値のin vitro上昇に関する検討 (2017)
  • Author(s): 渡部 多真紀，富岡 直子，土屋 雅勇，細山田 真
  • Organizer: 第50回日本痛風・核酸代謝学会
  • Place of Presentation: 東京新宿
  • Year and Date: 2017-02-17
• [Presentation] 11.Urat1-Uox double knockout mice are experimental animal model of renal hypouricemia and exercise-induced acute kidney injury. (2015)
  • Author(s): Hosoyamada M, Tsurumi Y, Tomioka NH, Sekine Y, Morisaki T, Uchida S
  • Organizer: 16th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: New York, USA
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] 腎性低尿酸血症と運動後急性腎不全の疾患モデル動物としてのUrat1-Uox-ダブルノックアウトマウス (2015)
  • Author(s): 鶴見 ゆう、富岡 直子、関根 祐子、細山田 真
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18
• [Presentation] 腎性低尿酸血症1型疾患モデル動物としてのUrat1-Uox-double KOマウスの検討 (2015)
  • Author(s): 細山田 真、鶴見 ゆう、富岡 直子、関根 祐子、内田 俊也
  • Organizer: 第48回日本痛風・核酸代謝学会総会
  • Place of Presentation: 東京新宿
  • Year and Date: 2015-02-20
• [Presentation] 尿酸トランスポーターURAT1遺伝子およびウリカーゼ遺伝子ダブルノックアウトマウスの尿酸動態 (2014)
  • Author(s): 細山田 真、鶴見 ゆう、富岡 直子、関根 祐子、内田 俊也
  • Organizer: 第44回日本腎臓学会東部学術大会
  • Place of Presentation: 東京新宿
  • Year and Date: 2014-10-24