Identification and characterization of the Ali18 mutation, which causes inflammatory arthritis in mice

2009 Fiscal Year Final Research Report

• Project/Area Number: 19500370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokai University
• Principal Investigator: ABE Koichiro Tokai University, 医学部, 講師 (90294123)
• Project Period (FY): 2007 – 2009
• Keywords: 病態モデル

Research Abstract

マウスでランダムに突然変異を誘発させることで、炎症性関節炎を引き起こすAli18系統が確立された。Ali18変異を同定するために、遺伝的解析及び候補遺伝子のDNA配列の決定を行った。その結果、第4番染色体に位置するリン酸化酵素のコード領域に突然変異が検出された。リン酸化は細胞のシグナル伝達に関係があり、Ali18変異による増殖シグナルの増幅が関節炎発症に関与すると考えられた。また、Ali18シグナルを阻害すれば炎症を抑制できる効果が期待された。

Research Products

• [Journal Article] Akira Narita, Tetsuaki Kimura, Kenji Imai, Minoru Kimura, Isabel Rubio-Aliaga, Sibylle Wagner, Thilo Jakob, Martin Hrabe de Angelis (2009)
  • Author(s): 阿部幸一郎, Matthias Klaften
  • Journal Title: Genome-wide search for genes that modulate inflammatory arthritis caused by A1118 mutation in mice Mammalian Genome Vol. 20 Pages: 152-161
  • Peer Reviewed
• [Journal Article] Ryoji Ikeda, Sumi Mizuno, Yoshihiro Uno, Sanae Ogiwara, Masato Ohtsuka, Ayako Isotani, Masaru Okabe, Kenji Imai, Junji Takeda (2009)
  • Author(s): Chikarra Kokubu, Kyoji Horie, 阿部幸一郎
  • Journal Title: A transposon-based chromosomal engineering method to survey a large cis-landscape in mice、Nature Genetics Vol. 41 Pages: 946-952
  • Peer Reviewed
• [Journal Article] Characterization of phospholipase gamma C enzymes with gain-of-mutations (2009)
  • Author(s): Katy Everett, Tom D Bunney, Youngdae Yoon, Fernando Rodoriguez Lima, Richard Harris, Paul C Driscoll, 阿部幸一郎, Helmut Fuchs, Martin Hrabe de Angelis, Phillip Yu, Wohnwa Cho, Matilda Katan
  • Journal Title: Journal of Biological Chemistry Vol. 284 Pages: 2083-2093
  • Peer Reviewed
• [Journal Article] Mammalian mutant resources for therapeutic challenges (2009)
  • Author(s): 阿部幸一郎, Phitipp Yu
  • Journal Title: Current Pharmaceutical Biotechnolog Vol. 10 Pages: 252-260
  • Peer Reviewed
• [Journal Article] Mammalian mutant resources for therapeutic challenges (2009)
  • Author(s): 阿部幸一郎, Minoru Kimura, Ken-ichi Yamamura
  • Journal Title: Current Pharmaceutical Biotechnology Vol. 10 Pages: 197
• [Journal Article] Hrabede Angelis Novel lymphocyte-independent mechanisms to initiate inflammatory arthritis via bone marrow-derived cells of A1118 mutant mice (2008)
  • Author(s): 阿部幸一郎, S. Wechs, S. Kalaydjiev, T. J. Franz, D. H. Busch, H. Fuchs,D. Soewarto, H. Behrendt, S. Wagner, T. Jakob, M.
  • Journal Title: Rheumatology Vol. 47 Pages: 292-300
  • Peer Reviewed
• [Journal Article] Leticia Quintanilla-Martinez, Gabriele Holzwimmer, Miep Helfrich, Eckhard Wolf, Stuart H. Ralston, Martin Hrabede Angelis, ER stress-mdiated apoptosis in a new mouse model of osteogenesis imperfecta (2008)
  • Author(s): Thomas S. Lisse, Frank Thiele, Helmut Fuchs, Wolfgang Hans, Gerhard K. H. Przemeck, 阿部幸一郎, Birgit Rathkolb
  • Journal Title: PLoS Genetics Vol. 4 Pages: e7
  • Peer Reviewed
• [Journal Article] Przemeck, Johannes Beckers, and Martin Hrabede Angelis、A genetic screen for modifiers of the Deltal-dependent Notch signaling function in the mouse (2007)
  • Author(s): Isabel Rubio-Aliaga, Dian Soewarto, Sibylle Wagner, Mathias Klaften, Helmut Fuchs, Svetoslav Kalaydjiev, Dirk Busch, Martina Klempt, Birgit Rathkolb, Eckhard Wolf, 阿部幸一郎, Stefan Zeiser, Gerhard K. H.
  • Journal Title: Genetics Vol. 175 Pages: 1451-1463
  • Peer Reviewed
• [Journal Article] Helmut Fuchs, Martin Hrabe de Angelis, Isolation and characterization of the AGA2 mouse : A new murine model for osteogenesis imperfecta (2006)
  • Author(s): Thomas Lisse, 阿部幸一郎
  • Journal Title: Calcified Tissue International Vol. 78, Suppl. 1 Pages: 5166-167
  • Peer Reviewed
• [Presentation] Martin Hrabe de Angelis, Alil8 変異マウスの炎症性関節炎を修飾する遺伝子群のゲノムワイドな探索 (2009)
  • Author(s): 阿部幸一郎, Mathias Klaften, 成田暁, 木村哲晃, 木村穣, Isabel Rubio-Aliaga, Sibylle Wagner, Thilo Jakob
  • Organizer: 第56回日本実験動物学会総会
  • Place of Presentation: 大宮
  • Year and Date: 20090000
• [Presentation] Martin Hrabe de Angelis, A novel ENU-induced mutation in phospholipase C gamma 2 causes inflammatory arthritis, metabolic defects, and in vitro infertility in the mouse (2009)
  • Author(s): 阿部幸一郎, Helmut Fuchs, Auke Boersma, Philipp Yu, Svetoslav Kalaydjiev, Matthias Klaften, Thure Adler, Wolfgang Hans, Birgit Rathkolb, Cornelia Prehn, Jurek Adamski, Dirk Busch, Eckhard Wolf, Valerie Gailus Durner, Matilda Katan, Susan Marschall, Sibylle Wagner
  • Organizer: 23rd International Mammalian Genome Conference
  • Place of Presentation: La Jolla, California
  • Year and Date: 20090000
• [Presentation] Martin Hrabe de Angelis 炎症性関節炎を呈するAli18変異マウスにおけるリンパ球非依存的病態発症機構 (2008)
  • Author(s): 阿部幸一郎, Sabine Wechs, Svetoslav Kalaydjiev, Tobias Franz, Dirk Busch, Helmut Fuchs, Dian Soewarto, Sibylle Wagner Thilo Jakob
  • Organizer: 第55回日本実験動物学会総会
  • Place of Presentation: 仙台
  • Year and Date: 20080000
• [Presentation] により誘発された新規炎症性疾患モデルAli18変異マウスの解析 (2007)
  • Author(s): 阿部幸一郎, Fuchs H, Lisse T, Hans W, Imai K, Hrabe de Angelis M, ENU
  • Organizer: 第54回日本実験動物学会総会
  • Place of Presentation: 東京
  • Year and Date: 20070000
• [Presentation] Hrabe de Angelis M, Genome-wide search for genes which modulate inflammatory arthritis caused by Ali18 mutation in mice (2007)
  • Author(s): 阿部幸一郎, Klaften M, Jakob T, 成田暁, 今井賢治, Rubio-Aliaga I, Wagner S
  • Organizer: 21st International Mammalian Genome Conference
  • Place of Presentation: Kyoto Japan
  • Year and Date: 20070000
• [Remarks]
  • URL: http://abe.med.u-tokai.ac.jp/index.html
• [Patent(Industrial Property Rights)] 炎症性疾患又は骨粗鬆症のスクリーニング方法 (2010)
  • Inventor(s): 阿部幸一郎、マーティン フラベデ アンゲリス、 ヘルムット フックス
  • Industrial Property Rights Holder: 学校法人東海大学
  • Industrial Property Number: 特許特願2010-165551
  • Filing Date: 2010-07-23