Generation of claudin targeted autoimmune disease mouse model

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659172
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: TSUKITA Sachiko 大阪大学, 生命機能研究科, 教授 (00188517)
• Project Period (FY): 2011 – 2012
• Keywords: 上皮細胞 / タイトジャンクション / 自己免疫疾患 / 自己抗体 / クローディン

Research Abstract

Autoimmune diseases, in which tissues of the body are pathologically attacked by an individual`s own immune system, are presently difficult to cure completely. Autoimmunogens are suggested to exist in almost all known autoimmune diseases, but their identity is not known in many cases. Notably, many autoimmune diseases are accompanied by inflammation in epithelial tissues. In this project, we propose that claudin, a major tight junction protein, is a target immunogen in some autoimmune diseases. To clarify the relationship between claudin and autoimmune diseases, we sought to generate a claudin-targeted autoimmune disease mouse model.

Research Products

• [Journal Article] Ezrin is required for thefunctional regulation of the epithelial sodium proton exchanger, NHE3 (2013)
  • Author(s): Hayashi, H., Tamura, A., Krishnan, D., Tsukita, S., Suzuki, Y., Kocinsky, HS., Aronson, PS., Orlowski, J., Grinstein, S., and Alexander, RT.
  • Journal Title: Plos One Volume: 8 Pages: e55623
  • DOI: doi:10.1371/journal.pone.0055623.
  • Peer Reviewed
• [Journal Article] Loss of claudins 2 and 15 from mice causes defects in paracellular Na(+) flow and nutritient transport in gut nad leads to death from malnutrition (2013)
  • Author(s): Wada, M., Tamura, A., Takahashi, N., and Tsukita, S.
  • Journal Title: Gastroenterology Volume: 114 Pages: 369-380
  • DOI: doi:ppii:S0016-5085(12)01551-X
  • Peer Reviewed
• [Journal Article] EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins (2012)
  • Author(s): Lei, Z., Maeda, T., Tamura, A., Nakamura, T., Yamazaki, Y., Shiratori, H., Yashiro, K., Tsukita, S., and Hamada, H
  • Journal Title: Dev Biol Volume: 15 Pages: 136-145
  • DOI: doi:10.1016/j.ydbio.2012.07.005
  • Peer Reviewed
• [Journal Article] Moesin-deficient mice reveal a non-redundant role for moesin in lymphocyte homeostasis (2012)
  • Author(s): Hirata, T., Nomachi, A., Tohya, K., Miyasaka, M., Tsukita, S., Watanabe, T., and Narumiya, S
  • Journal Title: Int Immunol Volume: 24 Pages: 705-717
  • DOI: doi:10.1093/intimm/dxs077.
  • Peer Reviewed
• [Journal Article] Claudin-cased paracellular proton barrier in the stomach (2012)
  • Author(s): Tamura, A., Yamazaki, Y., Hayashi, D., Suzuki, K., Sentani, K., Yasui, W., and Tsukita, S.
  • Journal Title: Ann NY Acad Sci Volume: 1258 Pages: 108-114
  • DOI: doi:10.1111/j.1749-6632.2012.06570.x.
  • Peer Reviewed
• [Journal Article] Rho GTP exchange factor ARHGEF11 regulates the integrity of epithelial juncrtions by connecting ZO-1 and RhoA-myosin II signaling (2012)
  • Author(s): Itoh, M., Tsukita, S., Yamazaki, Y., and Sugimoto, H.
  • Journal Title: Proc Natl Acad Sci USA. Volume: 109 Pages: 9905-9910
  • DOI: doi:10.1073/pnas.1115063109
  • Peer Reviewed
• [Presentation] Odf2 organizes two distinct appendage structures/functions in centrosomes and basalbodies (2013)
  • Author(s): Kazuhiro Tateishi
  • Organizer: Computational Cell Biology: The Interplay between Models and Experimentation
  • Place of Presentation: Cold Spring Harbor Laboratory, USA
  • Year and Date: 20130319-21
• [Presentation] Clitical Role of Basal Feet in Coorninated Ciliary Beating (2012)
  • Author(s): Sachiko Tsukita
  • Organizer: ASCB annual meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20121215-19
• [Presentation] Molecular mechanisms of cell morphogenesis (2012)
  • Author(s): 月田早智子
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 20121214-16
• [Presentation] Tight Junction-based Building of Biological Systems (2012)
  • Author(s): Sachiko Tsukita
  • Organizer: 第33回日本肥満学会
  • Place of Presentation: ホテルグランヴィア京都
  • Year and Date: 20121011-12
• [Presentation] Tight Junction-based Building of Biological Systems (2012)
  • Author(s): Sachiko Tsukita
  • Organizer: 上皮バリアと上皮輸送に関する国際シンポジウム
  • Place of Presentation: 立命館大学びわ国際キャンパス
  • Year and Date: 20120915-16
• [Presentation] 上皮細胞間タイトジャンクションを起点とした生体システムの構築 (2012)
  • Author(s): 月田早智子
  • Organizer: 第21回日本バイオイメージング学会学術集会
  • Place of Presentation: 京都国際会館
  • Year and Date: 20120827-28
• [Presentation] Claudin species-specific biological functions in Digestive Epithelial Cells (2012)
  • Author(s): Sachiko Tsukita
  • Organizer: International Conference Molecular Structure and Function of the Apical Junctional Complex in Epithelia and Endothelia.
  • Place of Presentation: Hyatt Regency Hotel in Merida, Mexico
  • Year and Date: 2012-12-14
• [Remarks] ホームページ
  • URL: http://www.fbs.osaka-u.ac.jp/labs/tsukita/