The analysis of the mechanism for tissue specificity autoimmune

• Project/Area Number: 18590473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Tsurumi University (2007); The University of Tokushima (2006)
• Principal Investigator: KURODA Noriyuki Tsurumi University, School of Dental Medicine, assistant professor (50359915)
• Co-Investigator(Kenkyū-buntansha): 松本 満 徳島大学, 分子酵素学研究センター, 教授 (60221595)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: autoimmune / diabetes / NOD mouse / AIRE / 胸腺上皮細胞 / 臓器特異性

Research Abstract

We established NOD background Aire deficient mice. All of the case, they have the growth problems until 7-8 weeks old. Using pathologenetic analysis, we can't find the insulitis from these mice's pancreas, but heavy inflammatory in acinus region around the islet of Langerhans. About 6% of Aire^<+/+> NOD mice developed the diabetes until 20 weeks old but we couldn't find any diabetes from Aire^+ NOD mice. In order to evaluate that Aire^+ NOD mice are intrinsically resistant to the development of diabetes, we used an induced diabetes model. We treated the mice with Cyclophosphamide (CY), which accelerates to develop diabetes in NOD mice. Most of the control Aire^<+/+> NOD mice develop the diabetes between 11 and 27 days after the injection of CY. But on the Aire+ NOD mice, there is no mice developed diabetes. These results strongly suggest Aire^+ NOD mice have the registration against developing diabetes.

Research Products

• [Journal Article] Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology (2008)
  • Author(s): Mitsuru Matsumoto, Yiqing Zhou, Shinji Matsuo, Hideki Nakanishi, Kenji Hirose, Hajimu Oura, Seiji Arase, Akemi Ishida-Yamamoto, Yoshimi Bando, Keisuke Izumi, Hiroshi Kiyonari, Naoko Oshima, Rika Nakayama, Akemi Matsushima, Fumiko Hirota, Yasuhiro Mouri, Noriyuki Kuroda, Shigetoshi Sano, and David D.Chaplin
  • Journal Title: Proceedings of the National Academy of Sciences 105 Pages: 6720-6724
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology (2008)
  • Author(s): Mitsuru Matsumoto, Yiqing Zhou, Shinji Matsuo, Hideki Nakanishi, Kenji Hirose, Hajimu Oura, Seiji Arase, Akemi Ishida-Yamamoto, Yoshimi Bando, Keisuke Izumi, Hiroshi Kiyonari, Naoko Oshima, Rika Nakayama, Akemi Matsushima, Fumiko Hirota, Yasuhiro Mouri, Noriyuki Kuroda, Shigetoshi Sano, David D. Chaplin
  • Journal Title: Proceedings of the National Academy of Sciences 105 Pages: 6720-6724
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice (2006)
  • Author(s): Shino Niki, Kiyotaka Oshikawa, Yasuhiro Mouri, Fumiko Hirota, Akemi Matsushima, Masashi Yano, Hongwei Han, Yoshimi Bando, Keisuke Izumi, Masaki Matsumoto, Keiichi I.Nakayama, Noriyuki Kuroda, and Mitsuru Matsumoto
  • Journal Title: The Journal of Clinical Investigation 116 Pages: 1292-1301
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Essential Role of I_κB Kinase (IKK) α in Thymic Organogenesis Required for the Establishment of Self-Tolerance (2006)
  • Author(s): Dan Kinoshita, Fumiko Hirota, Tsuneyasu Kaisho, Michiyuki Kasai, Keisuke Izumi, Yoshimi Bando, Yasuhiro Mouri, Akemi Matsushima, Shino Niki, Hongwei Han, Kiyotaka Oshikawa, Noriyuki Kuroda, Masahiko Maegawa, Minoru Irahara, Kiyoshi Takeda, Shizuo Akira, and Mitsuru Matsumoto
  • Journal Title: The Journal of Immunology 176 Pages: 3995-4002
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice (2006)
  • Author(s): Shino Niki, Kiyotaka Oshikawa, Yasuhiro Mouri, Fumiko Hirota, Akemi Matsushima, Masashi Yano, Hongwei Han, Yoshimi Bando, Keisuke Izumi, Masaki Matsumoto, Keiichi I. Nakayama, Noriyuki Kuroda, Mitsuru Matsumoto
  • Journal Title: The Journal of Clinical Investigation 116 Pages: 1292-1301
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Essential Role of I_k B Kinase(IKK) α in Thymic Organogenesis Required for the Establishment of Self-Tolerance (2006)
  • Author(s): Dan Kinoshita, Fumiko Hirota, Tsuneyasu Kaisho, Michiyuki Kasai, Keisuke Izumi, Yoshimi Bando, Yasuhiro Mouri, Akemi Matsushima, Shino Niki, Hongwei Han, Kiyotaka Oshikawa, Noriyuki Kuroda, Masahiko Mae gawa, Minoru Irahara, Kiyosbi Takeda, Shizuo Akira, Mitsuru Matsumoto
  • Journal Title: The Journal of Immunology 176 Pages: 3995-4002
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice. (2006)
  • Author(s): Niki, S., et al.
  • Journal Title: Journal of Clinical Investigation 116 Pages: 1292-1301
• [Journal Article] Essential role of IκB kinase α in thymic organogenesis required for the establishment of self-tolerance. (2006)
  • Author(s): Kinoshita, D., et al.
  • Journal Title: Jounal of Immunology 176 Pages: 3995-4002
• [Journal Article] Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology
  • Author(s): Mitsuru Matsumoto, Yiqing Zhou, Shinji Matsuo, Hideki Nakanishi, Kenji Hirose, Hajimu Oura, Seiji Arase, Akemi Ishida-Yamamoto, Yoshimi Bando, Keisuke Izumi, Hiroshi Kiyonari, Naoko Oshima, Rika Nakayama, Akemi Matsushima, Fumiko Hirota, Yasuhiro Mouri, Noriyuki Kuroda, Shigetoshi Sano, and David D.
  • Journal Title: Proceedings of the National Academy of Sciences (in press)
  • Peer Reviewed