Responsible genes for the aberrant production of MPO-ANCA

• Project/Area Number: 23510244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2012-2014); Jichi Medical University (2011)
• Principal Investigator: HAMANO Yoshitomo 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (10281354)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: SCG/Kj / MPO-ANCA / 血管炎 / 半月体形成性糸球体腎炎 / マッピング / ANCA関連血管炎 / 自己免疫 / 自己免疫疾患

Outline of Final Research Achievements

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse is a unique model of vasculitis with production of MPO-ANCA. Genome wide mapping revealed the non-Fas susceptibility locus of MPO-ANCA on chromosome 1, designated as Man-1. The aim of this study is to identify the responsible gene (s) of Man-1. Interval mapping created single peak of LOD curve on the Gene A, a protein-coding gene with unknown function. Because of the highest LOD score, Gene A was the first positional candidate gene. Recombinant Gene A accelerated the proliferation of murine myeloid cell line Mcl33D. However, transfection of Gene A to Mcl33D did not influenced to expression levels of leukocyte activation markers.
We established SCG/Kj-derived interval congenic mice with B6 background. Fortunately, we obtained mice with recombination between B6 and SCG/Kj at the midpoint of Man-1 interval. These mice will help us to narrow down positional candidate genes on Man-1 interval.

Research Products

• [Journal Article] Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan. (2014)
  • Author(s): Furuta, S., Chaudhry, AN., Hamano, Y., Fujimoto, S., Nagafuchi, H., Makino, H., Matsuo, S., Ozaki, S., Endo, T., Muso, E., Ito, C., Kusano, E., Yamagata, M., Ikeda, K., Kashiwakuma, D., Iwamoto, I., Westman, K. and Jayne, D.
  • Journal Title: J Rheumatol. Volume: 41(2) Issue: 2 Pages: 325-33
  • DOI: 10.3899/jrheum.130602
  • Peer Reviewed / Open Access
• [Journal Article] A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis (2014)
  • Author(s): Suzuki K, Nagao T, Itabashi M, Hamano Y, Sugamata R, Yamazaki Y, Yumura W, Tsukita S, Wang PC, Nakayama T, Suzuki K
  • Journal Title: Nephrol Dial Transplant Volume: 29 Issue: 6 Pages: 1168-1177
  • DOI: 10.1093/ndt/gft469
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Susceptibility QTLs for pathogenic leukocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model. (2014)
  • Author(s): Hamano Y, Abe M, Matsuoka S, Zhang D, Kondo Y, Kagami Y, Ishigami A, Maruyama N, Tsuruta Y, Yumura W, Suzuki K
  • Journal Title: Clin Exp Immunol. Volume: 2014 Mar 24. Issue: 1 Pages: 353-365
  • DOI: 10.1111/cei.12333
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenic leukocytosis and their susceptibility QTLs for vasculitis and crescentic glomerulonephritis in a model of SCG/Kj mice. (2013)
  • Author(s): Hamano, Y., Yumura, W., Maruyama, N., Suzuki, K.
  • Journal Title: La Presse Medicale & Quarterly Medical Review Volume: 42(4) Pages: 687-687
  • Peer Reviewed
• [Journal Article] A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis. (2013)
  • Author(s): Suzuki K, Nagao T, Itabashi M, Hamano Y, Sugamata R, Yamazaki Y, Yumura W, Tsukita S, Wang PC, Nakayama T, Suzuki K.
  • Journal Title: Nephrol Dial Transplant. Volume: 2013 Dec 5.
  • Peer Reviewed
• [Journal Article] Rituximab Treatment for PR3-ANCA-Positive Membranoproliferative Glomerulonephritis Associated with Adult-Onset Periodic Fever Syndrome. (2012)
  • Author(s): Hamano Y, Yoshizawa H, Sugase T, Miki T, Ohtani N, Hanawa S, Takeshima E, Morishita Y, Saito O, Takemoto F, Muto S, Yumura W, Kusano, E.
  • Journal Title: Case Reports in Nephrol Urol Volume: 2 Pages: 92-101
  • Peer Reviewed
• [Journal Article] Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice (2011)
  • Author(s): Zhang D, Kobayashi T, Hino O, et al
  • Journal Title: Cancer Sci Volume: 102(4) Issue: 4 Pages: 720-7
  • DOI: 10.1111/j.1349-7006.2011.01846.x
  • NAID: 10029291977
  • Peer Reviewed
• [Presentation] 腎疾患における抗moesin抗体の病的意義 (2014)
  • Author(s): 濱野慶朋、鶴田悠木、佐野夏帆、丸山直記、湯村和子、佐々木裕子、亀岡洋祐、鈴木和男
  • Organizer: 第57回 日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜会議センター（横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 腎動脈狭窄症とC型肝炎に合併した大量タンパク尿の一例 (2013)
  • Author(s): 濱野慶朋、佐野夏帆、勒寺紀栄、久保里奈、鶴田悠木、湯村和子
  • Organizer: 第18回板橋区医師会医学会
  • Place of Presentation: 板橋区民会館
• [Presentation] MPO-ANCA関連血管炎自然発症モデルマウスにおける腎炎・自己免疫形質とサイトカイン動態との関連 (2012)
  • Author(s): 濱野慶朋、長尾朋和、吉澤寛道、草野英二、鈴木和男、湯村和子
  • Organizer: 日本腎臓学会総会
  • Place of Presentation: 横浜
• [Presentation] 顆粒球吸着療法(GCAP)で解熱・軽快した成人発症型周期性発熱症候群の一例 (2012)
  • Author(s): 濱野慶朋、吉澤寛道、大谷尚子、三木拓也、武島えり、斉藤修、森下義幸、湯村和子、武藤重明、竹本文美、草野英二
  • Organizer: 日本透析医学会総会
  • Place of Presentation: 札幌
• [Presentation] Genomics and Genetics in ANCA-associated Vasculitis. (2012)
  • Author(s): Yoshitomo Hamano
  • Organizer: The Asia Pacific Meeting of Vasculitis and ANCA Workshop(招待講演)
  • Place of Presentation: Shinagawa, Tokyo, Japan
• [Presentation] Role of IL-17/IL-23 axis and pro-inflammatory cytokines in the pathogenesis of spontaneously occurring glomerulonephritis in a model of SCG/Kj mice. (2012)
  • Author(s): Yoshitomo Hamano, Tomokazu Nagao, Kazuo Suzuki, Hiromichi Yoshizawa, Eiji Kusano and Wako Yumura
  • Organizer: The Asia Pacific Meeting of Vasculitis and ANCA Workshop
  • Place of Presentation: Shinagawa, Tokyo, Japan
• [Book] 見逃すと怖い血管炎 (2014)
  • Author(s): 濱野慶朋、湯村和子
  • Total Pages: 170
  • Publisher: 日本医事新報社
• [Book] ループス腎炎．In安田隆（編）臨床腎臓内科学 (2013)
  • Author(s): 濱野慶朋、湯村和子
  • Total Pages: 12
  • Publisher: 南山堂
• [Book] 膠原病・RA・オーバーラッピング症候群と腎障害．安田隆（編）臨床腎臓内科学 (2013)
  • Author(s): 濱野慶朋、湯村和子
  • Total Pages: 3
  • Publisher: 南山堂
• [Book] 強皮症腎．安田隆（編）臨床腎臓内科学 (2013)
  • Author(s): 濱野慶朋、湯村和子
  • Total Pages: 5
  • Publisher: 南山堂
• [Book] 新領域別症候群シリーズ 血管炎 V. ANCA関連血管炎の病因・病理、診断・治療 1. ANCA関連血管炎（AAV)の基礎研究から臨床へのアプローチ (1)ゲノミクスと遺伝子解析 疾患モデルマウスによる疾患関連遺伝子の解析. (2013)
  • Author(s): 濱野慶朋、丸山直記、湯村和子、鈴木和男
  • Total Pages: 10
  • Publisher: 日本臨床社
• [Book] 新領域別症候群シリーズ No. 18 腎臓症候群（第2版）下巻 －その他の腎臓疾患を含めて－ XII 各種病態にみられる腎障害 造血器疾患 多発性骨髄腫 (2012)
  • Author(s): 濱野慶朋、湯村和子
  • Total Pages: 7
  • Publisher: 日本臨床社
• [Book] CKD（主に保存期腎不全）の患者さんの管理．Q&A21．高齢者に多い急速進行性糸球体腎炎ってどんな病気なの？ (2012)
  • Author(s): 濱野慶朋
  • Total Pages: 4
  • Publisher: 日本医事新報社
• [Book] 別冊日本臨床 新領域別症候群シリーズ No. 18 腎臓症候群（第2版） (2012)
  • Author(s): 濱野慶朋、湯村和子
  • Total Pages: 8
  • Publisher: 日本臨床社
• [Remarks] 東京都健康長寿医療センター 研究所
  • URL: http://www.tmghig.jp/J_TMIG/J_index.html