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

• 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)
• Co-Investigator(Kenkyū-buntansha): 今井 賢治 東海大学, 医学部, 教授 (70193646)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 病態モデル / 実験動物学 / 関節炎 / 炎症 / ポジショナルクローニン / 遺伝学 / 国際情報交換 / ドイツ / ポジショナルクローニング / マウス / 実験動物 / 病熊モデル / 炎症性関節炎 / 乾癬性関節炎 / ENU

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: 197-197
• [Journal Article] Positonal Cloning in mice and its use for molecular dissection of inflammatory arthritis (2009)
  • Author(s): Abe K, Yu P(2人中1番目)
  • Journal Title: Current Pharmaceutical Biotechnology 10 Pages: 252-260
  • Peer Reviewed
• [Journal Article] Mammalian mutant resources for therapeutic challenges (2009)
  • Author(s): Abe K, Kimura M, Yamamura K-I(3人中1番目)
  • Journal Title: Current Pharmaceutical Biotechnology 10 Pages: 197-197
• [Journal Article] A transposon-based chromosomal engineering method to survey a large cis-landscape in mice. (2009)
  • Author(s): Kokubu C, Horie K, Abe K, Ikeda R, et al.(12人中3番目)
  • Journal Title: Nature Genetics 41 Pages: 946-952
  • Peer Reviewed
• [Journal Article] Characterization of phospholipase gamma C enzymes with gain-of-function mutations. (2009)
  • Author(s): Driscoll PC, Abe K, Fuchs H, et al.(12人中7番目)
  • Journal Title: Journal of Biological Chemistry 284 Pages: 23083-23093
  • Peer Reviewed
• [Journal Article] Genome-wide search for genes that modulate inflammatory arthritis caused by Ali18 mutation in mice (2009)
  • Author(s): Abe K, Klaften M, Narita A, Kimura T, et al.(10人中1番目)
  • Journal Title: Mammalian Genome 20 Pages: 152-161
  • Peer Reviewed
• [Journal Article] Positional cloning in mice and its use for molecular dissection of inflammatory arthritis (2009)
  • Author(s): Koichiro Abe, Philipp Yu
  • Journal Title: Current Pharmaceutical Biotechnology 10 Pages: 252-260
  • Peer Reviewed
• [Journal Article] Genome-wide search for genes that modulate inflammatory arthritis caused by Ali18 mutation in mice (2009)
  • Author(s): K. Abe, M. Klaften, A. Narita, T. Kimura, K. Imai, et al.
  • Journal Title: Mammalian Genome 20 Pages: 152-161
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Novel lymphocyte mechanisms to initiate inflammatory arthri-tis via bone marrow-derrived cells of Ali18 mutatnt mice (2008)
  • Author(s): K. Abe, S. Wechs, S. Kalaydjiev, TJ. Franz, DH. Busch, et al.
  • Journal Title: Rheumatology 47 Pages: 292-300
  • Peer Reviewed
• [Journal Article] Novel lymphocyte -independent mechanisms to initiate inflammatory arthritis via bone marrow -derived cells of Ali18 mutant mice (2008)
  • Author(s): 阿部幸一郎, (他10名、1番目)
  • Journal Title: RHEUMATOLOGY 47 Pages: 292-300
  • Peer Reviewed
• [Journal Article] ER stress -mediated apoptosis in a new mouse model of osteogenesls imperfecta (2008)
  • Author(s): 阿部幸一郎, (他12名、6番目)
  • Journal Title: PLoS GENETICS 4
  • 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] A genetic screen for modifiers of the deltal -dependent notch signa ling function in the mouse (2007)
  • Author(s): 阿部幸一郎, (他14名、11番目)
  • Journal Title: GENETICS 106 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
• [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
• [Presentation] Ali18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、Matthias Klaften, 成田暁, ら(9人中1番目)
  • Organizer: 第56回日本実験動物学会総会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
• [Presentation] A novel ENU-induced mutation in phospholipase C gamma2 causes inflammatory arthritis, metabolic defects, and in vitro sperm infertility in the mouse (2009)
  • Author(s): Abe K, Fuchs H, Boersma A, et al.(18人中1番目)
  • Organizer: 23rd International Mammlian Genome Conference
  • Place of Presentation: LaJolla, CA, USA
• [Presentation] 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, S. Wechs, S. Kalaydjiev, T. Franz, et al.
  • Organizer: 第55回日本実験動物学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2008-05-15
• [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
• [Presentation] Genome-wide search for genes which modulate i nflammatory arthritis caused by Ali18m utation in mice (2007)
  • Author(s): 阿部幸一郎, (他7名、1番目)
  • Organizer: 21st International Mammalian Genome Conference
  • Place of Presentation: KYOTO TERRSA(京都)
  • Year and Date: 2007-10-29
• [Presentation] ENUにより誘導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, (他5名、1番目)
  • Organizer: 第54回日本実験動物学会総会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2007-05-23
• [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
• [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
• [Remarks]
  • URL: http://abe.med.u-tokai.ac.jp/index.html
• [Remarks]
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• [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: 2010-165551
  • Filing Date: 2010-07-23