Clarification of the pathogenesis of cyst formation in autosomal dominant polycystic kidney disease using a TRPP2 697fsX transgenic mouse model

• Project/Area Number: 23790936
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: YAMADA Kazunori 金沢大学, 医薬保健学総合研究科, 特任准教授 (90397224)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 常染色体優性多発性嚢胞腎 / モデルマウス / 多発性嚢胞腎 / PKD2 / 局在異常

Outline of Final Research Achievements

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder characterized by multiple cysts in both kidneys and other organs. We obtained TRPP2 697fsX, which causes the aberrant localization of polycystin-2, from a patient with ADPKD and established TRPP2 697fsX transgenic mice. These mice exhibited proteinuria, renal insufficiency at 4 weeks, and cyst formation at a minimum age of 6 months. These data indicate that TRPP2 697fsX transgenic mice can be used as mice models of ADPKD. Hence, using these models, we will further analyze the mechanism underlying cyst formation in ADPKD.

Research Products

• [Journal Article] A case developing minimal change disease during the course of IgG4-related disease. (2015)
  • Author(s): Yamada K, Zoshima T, Ito K, Mizushima I, Hara S, Horita S, Nuka H, Hamano R, Fujii H, Yamagishi M, Kawano M.
  • Journal Title: Mod Rheumatol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Primary Sjogren's syndrome with chronic tubulointerstitial nephritis and lymphadenopathy mimicking IgG4-related disease. (2014)
  • Author(s): Kawano M, Suzuki Y, Yamada K, Mizushima I, Matsumura M, Nakajima K, Yamagishi M, Yamaguchi Y.
  • Journal Title: Mod Rheumatol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Situs inversus and cystic kidney disease: Two adult patients with this heterogeneous syndrome. (2013)
  • Author(s): Onoe T, Konoshita T et al.
  • Journal Title: Am J Case Rep Volume: 14 Pages: 20-25
  • DOI: 10.12659/ajcr.883751
  • NAID: 120006319210
  • Peer Reviewed
• [Journal Article] Galactosylation of IgG1 modulates FcγRIIB-mediated inhibition of murine autoimmune hemolytic anemia. (2013)
  • Author(s): Yamada K, Ito K, Furukawa J, Nakata J, Alvarez M, Verbeek JS, Shinohara Y, Izui S
  • Journal Title: J Autoimmun Volume: 47 Pages: 104-110
  • DOI: 10.1016/j.jaut.2013.09.001
  • Peer Reviewed
• [Journal Article] Investigations of IgG4-related disease involving the skin (2013)
  • Author(s): Yamada K, Hamaguchi Y, Saeki T, Yagi K, Ito N, Kakuchi Y, Yamagishi M, Takehara K, Nakanuma Y, Kawano M
  • Journal Title: Mod Rheumatol Volume: 23(5) Issue: 5 Pages: 986-93
  • DOI: 10.1007/s10165-012-0786-7
  • NAID: 10031201158
  • Peer Reviewed
• [Journal Article] Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis. (2013)
  • Author(s): Yamada K, Hamaguchi Y, Saeki T, Yagi K, Ito N, Kakuchi Y, Yamagishi M, Takehara K, Nakanuma Y, Kawano M.
  • Journal Title: Mod Rheumatol Volume: Epub 2012 Nov 1
  • NAID: 10031127240
  • Peer Reviewed
• [Journal Article] Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis. (2012)
  • Author(s): Mizushima I, Yamada K, Fujii H, Inoue D, Umehara H, Yamagishi M, Yamaguchi Y, Nagata M, Matsumura M, Kawano M
  • Journal Title: Mod Rheumatol Volume: 22（6） Pages: 859-570
  • NAID: 10031127240
  • Peer Reviewed
• [Journal Article] IgG4-related tubulointerstitial nephritis and hepatic inflammatory pseudotumor without hypocomplementemia. (2011)
  • Author(s): Kim F, Yamada K, Inoue D, Nakajima K, Mizushima I, Kakuchi Y, Fujii H, Narumi K, Matsumura M, Umehara H, Yamagishi M, Kawano M.
  • Journal Title: Intern Med Volume: 50(11) Pages: 1239-44
  • NAID: 130000770479
  • Peer Reviewed
• [Journal Article] IgG4-related skin lesions in a patient with IgG4-related chronic sclerosing dacryoadenitis and sialoadenitis. (2011)
  • Author(s): Kakuchi Y, Yamada K, Suzuki Y, Ito N, Yagi K, Matsumura M, Yamagishi M, Umehara H, Zen Y, Hasegawa M, Takehara K, Kawano M.
  • Journal Title: Intern Med Volume: 50(14): Pages: 1465-1469
  • NAID: 130000969423
  • Peer Reviewed
• [Journal Article] Pneumococcal vertebral osteomyelitis and psoas abscess in a patient with systemic lupus erythematosus disclosing positivity of pneumococcal urinary antigen assay. (2011)
  • Author(s): Matsumura M, Ito K, Kawamura R, Fujii H, Inoue R, Yamada K, Yamagishi M, Kawano M.
  • Journal Title: Intern Med Volume: 50(20) Pages: 2357-60
  • NAID: 130001087747
  • Peer Reviewed
• [Presentation] Clinical analysis of restless legs syndrome in long-term Japanese hemodialysis patients (2014)
  • Author(s): Kazunori Yamada, Toru Shibata, Toshiaki Kimura, Tsutomu Matsushima, Remon Otake, Akira Junicho, Masatsune Hasegawa, Mitsuhiro Kawano, Toru Hasegawa
  • Organizer: Kidney Week 2014
  • Place of Presentation: philadelphia, U.S.A.
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] IgG4関連疾患の経過中に微小変化型ネフローゼ症候群を発症した1例 (2014)
  • Author(s): 山田和徳、蔵島乾、伊藤清亮、堀田成人、額裕海、濱野良子、藤井博、川野充弘
  • Organizer: 第51回中部リウマチ学会
  • Place of Presentation: 朱鷺メッセ（新潟）
  • Year and Date: 2014-08-30
• [Presentation] 透析患者におけるレストレスレッグス症候群の臨床的検討 (2014)
  • Author(s): 山田和徳、柴田透、木村俊明、松島勉、大武礼文、十二町明、長谷川眞常、川野充弘、長谷川徹
  • Organizer: 第59回日本透析医学会学術集会・総会
  • Place of Presentation: 神戸ポートピアホテル（神戸）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Abundant APRIL-Producing Macrophages in IgG4-related Kidney Disease (2014)
  • Author(s): Kazunori Yamada, Takahiro Kawakami, Ichiro Mizushima, Ryoko Hamano, Hiroshi Fujii, Masakazu Yamagishi, and Mitsuhiro Kawano
  • Organizer: Second International Symposium on IgG4 & Related Disease
  • Place of Presentation: Sheraton Waikiki, Honolulu, U.S.A.
• [Presentation] 全内臓逆位を合併した嚢胞性腎疾患2例における遺伝学的検討 (2013)
  • Author(s): 小野江 為人，此下 忠志，山田 和徳，濱野 良子，水島 伊知郎，黒田 昌宏，鍵谷 聡志，川野 充弘
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] IgG4関連腎臓病におけるマクロファージ、APRILの関与 (2013)
  • Author(s): 水島伊知郎，山田 和徳，松永 貴弘，鈴木 康倫，川村 里佳，濱野 良子，藤井 博，松村 正巳，川野 充弘
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] IｇG4関連皮膚疾患の臨床的・病理学的検討 (2012)
  • Author(s): 山田和徳、佐伯敬子、川野充弘
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都）
• [Presentation] IgG4関連腎臓病におけるAPRIL発現の検討 (2012)
  • Author(s): 山田和徳、川上貴裕、水島伊知郎、鈴木康倫、藤井博、松村正巳、川野充弘
  • Organizer: 第21回シェーグレン症候群学術集会
  • Place of Presentation: ウェスティン都ホテル京都（京都府）
• [Presentation] マウスIgG1型抗赤血球抗体の解析
  • Author(s): 山田和徳
  • Organizer: 森シンポジウム 「次世代のイオンチャネル研究を考える会」(招待講演)
  • Place of Presentation: 京都ホテルエミナース（京都）
• [Presentation] 新規IgG4関連疾患モデルマウスの樹立
  • Author(s): 山田和徳、塚正彦、覚知泰志、藤井博、松村正巳、川野充弘
  • Organizer: 第20回日本シェーグレン症候群学会
  • Place of Presentation: ホテル金沢（金沢）
• [Presentation] Clinical utility of minor salivary gland biopsy to diagnose IgG4-related disease
  • Author(s): Kazunori Yamada, Mitsuhiro Kawano, Ichiro Mizushima, Satoshi Hara, Yasushi Kakuchi, Hiroshi Fujii, Yuko Waseda, Masayuki Takahira, Masakazu Yamagishi, and Masami Matsumura
  • Organizer: International IgG4-RD Symposium
  • Place of Presentation: Massachusetts General Hospital and the Holiday Inn Boston at Beacon Hill (Boston, USA)