Production of disease model mice for the drug screening of familial juvenile hyperuricemic nephropathy

• Project/Area Number: 20590547
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Keio University
• Principal Investigator: HOSOYAMADA Makoto Keio University, 薬学部, 准教授 (00291659)
• Co-Investigator(Renkei-kenkyūsha): ICHIDA Kimiyoshi 東京薬科大学, 薬学部, 教授 (80183169)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 薬物治療学 / 病態モデル / 病態モデル動物 / 高尿酸血症 / 腎臟 / 腎臓 / 病態モドル動物

Research Abstract

Pathophysiological mechanism of Familial Juvenile Hyperuricemic Nephropathy (FJHN) was investigated by production of the FJHN model mice, mutated human uromodulin gene transgenic mice. In the kidneys of the mice, it was observed that androgen action enhanced by increasing of Srd5a2 gene transcription should induce the transcription of Cyp4a12a gene, which causes renal cyst formation and renal damage ("nephropathy"), and that of Slc22a12 gene, which causes hyperuricemia.

Research Products

• [Journal Article] The effect of female hormones upon urate transport systems in the mouse kidney. (2011)
  • Author(s): Takiue Y, Hosoyamada M, Kimura M, Saito H
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. 30(2) Pages: 113-9
  • Peer Reviewed
• [Journal Article] Enhancement of Androgen Action in the Kidneys of Transgenic Mice Harboring the Mutant Human UMOD Gene. (2011)
  • Author(s): Takiue Y, Hosoyamada M, Kimura M, Saito H
  • Journal Title: J Pharmacol Sci. 115(3) Pages: 383-9
  • NAID: 10029892818
  • Peer Reviewed
• [Journal Article] Enhancement of Androgen Action in the Kidneys of Transgenic Mice Harboring the Mutant Human UMOD Gene. (2011)
  • Author(s): Takiue Y, Hosoyamada M
  • Journal Title: J Pharmacol Sci. Volume: 115 Pages: 383-389
  • NAID: 10029892818
  • Peer Reviewed
• [Journal Article] The effect of testosterone upon the urate reabsorptive transport system in mouse kidney. (2010)
  • Author(s): Hosoyamada M, Takiue Y, Shibasaki T, Saito H
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. 29(7) Pages: 574-579
  • Peer Reviewed
• [Journal Article] Development of LC-MS method for detection of mutant uromodulin protein. (2010)
  • Author(s): Yasuda M, Kaneko K, Hachisu H, Ochiai M, Yamanobe T, Mawatari K, Nakagomi K, Minoura N, Hosoyamada M
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. 29(4-6) Pages: 515-7
  • Peer Reviewed
• [Journal Article] Establishment and analysis of SLC22A12 (URAT1) knockout mouse. (2010)
  • Author(s): Hosoyamada M, Takiue Y, Morisaki H, Cheng J, Ikawa M, Okabe M, Morisaki T, Ichida K, Hosoya T, Shibasaki T
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. 29(4-6) Pages: 314-320
  • Peer Reviewed
• [Journal Article] The effect of testosterone upon the urate reabsorptive transport system in mouse kidney. (2010)
  • Author(s): Hosoyamada M
  • Journal Title: Nucleosides Nucleotides Nucleic Acids Volume: 29 Pages: 574-579
  • Peer Reviewed
• [Journal Article] Establishment and analysis of Slc22a12(Urat1)knockout mouse (2010)
  • Author(s): Hosoyamada M
  • Journal Title: Nucleosides Nucleotides Nucleic Acids 29(4-6) Pages: 314-320
  • Peer Reviewed
• [Journal Article] Production and characterization of transgenic mice harboring mutant human UMOD gene. (2008)
  • Author(s): Takiue Y, Hosoyamada M, Yokoo T, Kimura M, Ochiai M, Kaneko K, Ichida K, Hosoya T, Shibasaki T.
  • Journal Title: Nucleosides Nucleotides Nucleic Acids. 27 Pages: 596-600
  • Peer Reviewed
• [Journal Article] Progressive accumulation of intrinsic mouse uromodulin in the kidneys of transgenic mice harboring the mutant human uromodulin gene. (2008)
  • Author(s): Takiue Y, Hosoyamada M, Yokoo T, Kimura M, Shibasaki T
  • Journal Title: Biol Pharm Bull 31 Pages: 405-11
  • NAID: 110006623065
  • Peer Reviewed
• [Presentation] ウロモジュリンと家族性若年性高尿酸血症性腎症1型 (2011)
  • Author(s): 細山田真,滝上裕一,齋藤英胤
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] 家族性若年性高尿酸血症性腎症1型モデルマウス腎臓では5'-レダクターゼ2発現が増加する (2011)
  • Author(s): 細山田真,岩川奈々,滝上裕一,木村真規,齋藤英胤
  • Organizer: 第84回日本薬理学会
  • Place of Presentation: 横浜
• [Presentation] The effect of sex hormones upon urate transport systems in the mouse kidney. (2011)
  • Author(s): Takiue Y, Hosoyamada M, Kimura M, Saito H
  • Organizer: 14th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: PP11 Tokyo
• [Presentation] ウロモジュリンの遺伝子変異によるアンドロゲン作用の増加 (2011)
  • Author(s): 滝上裕一,細山田真,木村真規,齋藤英胤
  • Organizer: 第44回日本痛風・核酸代謝学会総会
  • Place of Presentation: 東京
• [Presentation] シンポジウム2「トランスポーター研究の最前線」腎臓における尿酸輸送 (2010)
  • Author(s): 細山田真
  • Organizer: 第54回日本薬学会関東支部大会
  • Place of Presentation: 東京
• [Presentation] 尿酸再吸収トランスポーターの性ホルモンによる発現調節 (2010)
  • Author(s): 滝上裕一,細山田真,木村真規,柴崎敏昭
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] 性ホルモンによる尿酸動態の変化 (2010)
  • Author(s): 滝上裕一,細山田真,木村真規,柴崎敏昭
  • Organizer: 第43回日本痛風・核酸代謝学会総会
  • Place of Presentation: 大阪
• [Presentation] Establishment and analysis of Slc22a12(Urat1)knockout mouse (2009)
  • Author(s): Hosoyamada M
  • Organizer: 13th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2009-06-24
• [Presentation] 家族性若年性高尿酸血症性腎症モデルマウスの腎臓における内因性マウスウロモジュリンの蓄積 (2009)
  • Author(s): 滝上 裕一, 細山田 真, 他
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-17
• [Presentation] Development of LC-MS method for detection of the mutated uromodulin. (2009)
  • Author(s): Yasuda M, Kaneko K, Hachisu H, Ochiai M, Yamanobe T, Mawatari K, Nakagomi K, Minoura N, Hosoyamada M
  • Organizer: 13th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: Stockholm, Sweden
• [Presentation] Single nucleotide polymorphisms in ABCG2 in Japanese hyperuricemic patients. (2009)
  • Author(s): Ichida K, Matsuo H, Hosoyamada M, Shinomiya N, Hosoya T
  • Organizer: 13th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: Stockholm, Sweden
• [Presentation] Establishment and analysis of Slc22a12 (Urat1) knockout mouse. (2009)
  • Author(s): Hosoyamada M, Morisaki H, Cheng J, Ikawa M, Okabe M, Morisaki T, Takiue Y, Ichida K, Hosoya T, Shibasaki T
  • Organizer: 13th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: Stockholm, Sweden
• [Presentation] LC-MSを用いた変異ウロモジュリン検出法の開発 (2009)
  • Author(s): 安田誠,蜂須広佳,落合真奈美,金子希代子,山辺智代,馬渡健一,中込和哉,箕浦憲彦,細山田真
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] ウロモジュリン蛋白の蓄積は遺伝子変異が原因である (2009)
  • Author(s): 滝上裕一,中込早苗,木村真規,細山田真,柴崎敏昭
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] 家族性若年性高尿酸血症性腎症モデルマウスの腎臓における内因性マウスウロモジュリンの蓄積 (2009)
  • Author(s): 滝上裕一,木村真規,細山田真,柴崎敏昭
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
• [Presentation] LC-MSを用いた変異ウロモジュリン検出法の開発 (2009)
  • Author(s): 安田誠,蜂須広佳,落合真奈美,金子希代子,山辺智代,藤森新,馬渡健一,中込和哉,箕浦憲彦,細山田真
  • Organizer: 第42回日本痛風・核酸代謝学会
  • Place of Presentation: 東京
• [Presentation] マウス尿酸トランスポーターmURAT1の性ホルモンによる発現調節機構 (2009)
  • Author(s): 滝上裕一,細山田真,木村真規,柴崎敏昭
  • Organizer: 第42回日本痛風・核酸代謝学会
  • Place of Presentation: 東京
• [Presentation] シンポジウム2「低尿酸血症の臨床的意義」低尿酸血症の分子メカニズム(Urat1ノックアウトマウスの作出と検討) (2009)
  • Author(s): 細山田真
  • Organizer: 第42回日本痛風・核酸代謝学会
  • Place of Presentation: 東京