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Generation of a disease model for epidermolysis bullosa acquisita using autoantigen-humanized mice and application for the development of novel treatment

Research Project

Project/Area Number 20591312
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionHokkaido University

Principal Investigator

SHIBAKI Akihiko  Hokkaido University, 大学院・医学研究科, 非常勤講師 (40291231)

Co-Investigator(Kenkyū-buntansha) AKIYAMA Masashi  名古屋大学, 大学院・医学系研究科, 教授 (60222551)
伊藤 圭  北海道大学, 大学院・医学研究科, 非常勤講師 (20421977)
Co-Investigator(Renkei-kenkyūsha) ITO Kei  北海道大学, 大学院・医学研究科, 非常勤講師 (20421977)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords皮膚病理学 / 免疫 / 治療 / 臨床 / 自己免疫性疾患 / 動物モデル / リンパ球 / 細胞・組織
Research Abstract

We tried to develop an active disease model for epidermolysis bullosa acquisita which produce IgG against human type VII collagen (COL7). Immunized wild type mice with recombinant human COL7 protein with adjuvant produced high titer of anti-human COL7 IgG antibody in vivo. We injected those IgG in neonatal COL7-humanized mice intraperitonealy. We observed the linear deposition of IgG at the basement membrane zone. To develop an active model for EBA, we generated immunodeficient COL7-humanized mice. Splenocytes isolated from immunized wild type mice were transferred into immunodeficient COL7-humanized mice. However, the recipient mice produced no anti-human COL7 IgG or developed no skin changes.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (22 results)

All 2010 2009 2008 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results) Presentation (6 results)

  • [Journal Article] Blockade of autoantibody-initiated tissue damage by using recombinant Fab antibody fragments against pathogenic autoantigen.2010

    • Author(s)
      Wang G, Ujiie H, Shibaki A, Nishie W, Tateishi Y, Kikuchi K, Li Q, McMillan JR, Morioka H, Sawamura D, Nakamura H, Shimizu H.
    • Journal Title

      American Journal of Pathology 176

      Pages: 914-25

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel active mouse model for bullous pmephigoid targeting humanized pathogenic antigen.2010

    • Author(s)
      Ujiie H, Shibaki A, Nishie W, Sawamura D, Wang G, Tateishi Y, Li Q, Moriuchi R, Qiao H, Nakamura H, Akiyama M, Shimizu H.
    • Journal Title

      Journal of Immunology 184

      Pages: 2166-74

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A domain induces blisters via complement activation in experimental bullous pemphigoid model.2010

    • Author(s)
      Li Q, Ujiie H, Shibaki A, Wang G, Moriuchi R, Qiao HJ, Morioka H, Shinkuma S, natsuga K, Long HA, Nishie W, Shimizu H.
    • Journal Title

      Journal of Immunology 185

      Pages: 7746-55

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] What's new in bullous pemphigoid.2010

    • Author(s)
      Ujiie H, Shibaki A, Nishie W, Shimizu H.
    • Journal Title

      Journal of Dermatology 37

      Pages: 194-204

    • NAID

      10027065912

    • Related Report
      2010 Final Research Report
  • [Journal Article] Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A domain induces blisters via complement activation in experimental bullous pemphigoid model.2010

    • Author(s)
      Li, Q, Shibaki A, et al.
    • Journal Title

      J Immunol

      Volume: 185 Pages: 17746-7755

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] What's new in bullous pemphigoid.2010

    • Author(s)
      Ujiie H, Shibaki A, et al.
    • Journal Title

      J Dermatol

      Volume: 37 Pages: 194-204

    • NAID

      10027065912

    • Related Report
      2010 Annual Research Report
  • [Journal Article] A novel active mouse model for bullous pmephigoid targeting humanized pathogenic antigen.2010

    • Author(s)
      Ujiie H, et al.
    • Journal Title

      J Immunol 184

      Pages: 2166-2174

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Collagen XVII participates in keratinocyte adhesion to collagen IV, and in p38-MAPK-dependetn migration and cell signaling.2009

    • Author(s)
      Qiao H, Shibaki A, Long HA, Wang G, Li Q, Nishie W, Abe R, Akiyama M, Shimizu H, McMillan JR.
    • Journal Title

      Journal of Investigative Dermatology 129

      Pages: 2288-95

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disseminated cutaneous Mycobacterium kansasii infection in a patient infected with the human immunoceficiency virus.2009

    • Author(s)
      Nomura Y, Nishie W, Shibaki A, Ibata M, Shimizu H.
    • Journal Title

      Clinical and Experimental Dermatology 34

      Pages: 625-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Keratinocyte-/fibroblast-targeted rescue of Col7a1-disrupted mice and generation of an exact dystrophic epidermolysis bullosa model using human COL7A1 mutation.2009

    • Author(s)
      Ito K, Sawamura D, Goto M, Nakamura H, Nishie W, Sakai K, Natsuga K, Shinkuma S, Shibaki A, Uitto J, Denton CP, Nakajima O, Akiyama M, Shimizu H.
    • Journal Title

      American Journal of Pathology 175

      Pages: 2508-17

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Keratinocyte-/fibroblast-targeted rescue of Col7a1-disrupted mice and generation of an exact dystrophic epidermolysis bullosa model using human COL7A1 mutation.2009

    • Author(s)
      Ito K, et al.
    • Journal Title

      Am J Pathol 176

      Pages: 2508-2517

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of autoantibody-initiated tissue damage by using recombinant Fab antibody fragments against pathogenic autoantigen.2009

    • Author(s)
      Wang G, et al.
    • Journal Title

      Am J Pathol 176

      Pages: 914-925

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cutaneous pemphigus vulgaris with skin features similar to the classic mucocutaneous type : a case report and review of the literature.2008

    • Author(s)
      Shinkuma S, Nishie W, Shibaki A, Sawamura D, Ito K, Tsuji-Abe Y, Natsuga K, Chan PT, Amagai m, Shimizu H.
    • Journal Title

      Clinical and Experimental Dermatology 33

      Pages: 724-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cutaneous pemphigus vulgaris with skin features similar to the classic mucocutaneous type : a case report and review of the literature2008

    • Author(s)
      Shinkuma S., et.al.
    • Journal Title

      Clin Exp Dermatol 33

      Pages: 724-728

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Collagen XVII participates in keratinocyte adhesion to collagen W, and in p38-MAPK-dependetn migration and cell signaling

    • Author(s)
      Qiao H., et.al.
    • Journal Title

      J Invest Dermatol (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disseminated Cutaneous Mycobacterium kansasii infection in a patient infected with the human immunoceficiency virus

    • Author(s)
      Nomura Y., et.al.
    • Journal Title

      Clin Exp Dermatol (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Human IgG1 mAb against human COL17 NC16A developed from BP patients induces blisters in experimental bullous pemphigoid model.2010

    • Author(s)
      Shibaki A.
    • Organizer
      Society for Investigative Dermatology Annual Meeting
    • Place of Presentation
      Hilton Atlanta, Atlanta, Georgia. (USA)
    • Year and Date
      2010-05-08
    • Related Report
      2010 Final Research Report
  • [Presentation] Human IgG1 mAb against human COL17 NC16A developed from BP patients induces blisters in experimental bullous pemphigoid model2010

    • Author(s)
      Shibaki A
    • Organizer
      Society for Investigative Dermatology Annual Meeting
    • Place of Presentation
      Hilton Atlanta, Atlanta, Georgia.(USA)
    • Year and Date
      2010-05-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pathomechanism in bullous pemphigoid- evidence from the model animal-.2009

    • Author(s)
      Shibaki A.
    • Organizer
      The 4^<th> Joint Meeting of Japanese Dermatological Association and Australasian College of Dermatologists
    • Place of Presentation
      札幌市
    • Year and Date
      2009-07-10
    • Related Report
      2010 Final Research Report
  • [Presentation] Pathomechanism in bullous pemphigoid- evidence from the model anima-2009

    • Author(s)
      Shibaki A
    • Organizer
      The 4^<th> Joint Meeting of Japanese Dermatological Association and Australasian College of Dermatologists
    • Place of Presentation
      北海道大学学術交流会館
    • Year and Date
      2009-07-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] Development of an active disease model for bullous pemphigoid.2008

    • Author(s)
      Ujiie H, Shibaki A, et al.
    • Organizer
      International Investigative Dermatology 2008
    • Place of Presentation
      京都市
    • Year and Date
      2008-05-17
    • Related Report
      2010 Final Research Report
  • [Presentation] Development of an active disease model for bullous pemphigoid2008

    • Author(s)
      Ujiie H., et.al.
    • Organizer
      International Investigative Dermatology 2008
    • Place of Presentation
      京都市
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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