• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Production of a novel blistering disease model by regulating expression of collagen XVII

Research Project

Project/Area Number 24390274
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Dermatology
Research InstitutionHokkaido University

Principal Investigator

Nishie Wataru  北海道大学, 医学(系)研究科(研究院), 准教授 (20443955)

Co-Investigator(Kenkyū-buntansha) UJIIE HIDEYUKI  北海道大学, 大学病院, 助教 (60374435)
SHINKUMA SATORU  北海道大学, 医学(系)研究科(研究院), 助教 (00613788)
NATSUGA KEN  北海道大学, 大学病院, 助教 (70645457)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords皮膚病態学 / 皮膚病理学 / 生体分子 / タンパク質 / 細胞・組織 / 酵素 / 自己免疫
Outline of Final Research Achievements

Collagen XVII (COL17) is a hemidesmosomal molecule which keeps adhesion between the epidermis and dermis. Loss of CO17 expression due to mutation in the COL17A1 leads to blistering disease, epidermolysis bullosa (EB); in addition, autoimmunity to COL17 results in autoimmune blistering disorder bullous pemphigoid (BP). The purpose of this study is to produce a novel blistering model by regulating COL17 expression based on Tet-on system. Transgenic mice carrying human COL17 cDNA driven under the CMV promoter with Tet response element and Tet transactivator sequences driven under the K14 promoter were produced. Upon oral administration of doxycycline (DOX), the Tg mice started to express human COL17 in basal keratinocytes, following by production of IgG autoantibodies directing human COL17. The Tg mice must be useful tool for elucidating pathogenesis of EB and BP, as well as for establishing therapies for these orphan diseases.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (14 results)

All 2016 2015 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Extracellular cleavage of collagen XVII is essential for correct cutaneous basement membrane formation.2016

    • Author(s)
      Nishimura M, Nishie W, Shirafuji Y, Shinkuma S, Natsuga K, Nakamura H, Sawamura D, Iwatsuki K, Shimizu H
    • Journal Title

      Hum Mol Genet

      Volume: 15;25(2) Issue: 2 Pages: 328-39

    • DOI

      10.1093/hmg/ddv478

    • NAID

      120005868259

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Context-Dependent Regulation of Collagen XVII Ectodomain Shedding in Skin.2015

    • Author(s)
      Nishie W, Natsuga K, Iwata H, Izumi K, Ujiie H, Toyonaga E, Hata H, Nakamura H, Shimizu H.
    • Journal Title

      Am J Pathol

      Volume: in press Issue: 5 Pages: 1361-71

    • DOI

      10.1016/j.ajpath.2015.01.012

    • NAID

      120005752843

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo analysis of IgE autoantibodies in bullous pemphigoid: A study of 100 cases.2015

    • Author(s)
      Moriuchi R, Nishie W, Ujiie H, Natsuga K, Shimizu H.
    • Journal Title

      J Dermatol Sci

      Volume: 78 Issue: 1 Pages: 21-25

    • DOI

      10.1016/j.jdermsci.2015.01.013

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Update on the pathogenesis of bullous pemphigoid: an autoantibody-mediated blistering disease targeting collagen XVII.2014

    • Author(s)
      Nishie W
    • Journal Title

      J Dermatol Sci

      Volume: 73 Issue: 3 Pages: 179-186

    • DOI

      10.1016/j.jdermsci.2013.12.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Infantile eczema caused by formula milk2013

    • Author(s)
      Ito T, Nishie W, Fujita Y, Abe R, Shimizu H
    • Journal Title

      Lancet

      Volume: 381 Issue: 9881 Pages: 1958-1958

    • DOI

      10.1016/s0140-6736(13)60684-4

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coiled-coils ensure the physiological ectodomain shedding of collagen XVII2012

    • Author(s)
      Nishie w, Jackow J, et al.
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 35 Pages: 29940-8

    • DOI

      10.1074/jbc.m112.345454

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antibodies to pathogenic epitopes on type XVII collagen cause skin fragility in a complement-dependent and-independent manner2012

    • Author(s)
      Natsuga K, Nishie W, et al.
    • Journal Title

      J Immunol

      Volume: 188 Pages: 5792-9

    • NAID

      10031131103

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circumscribed palmar hypokeratosis : Correlation between histopathological patterns and dermoscopic findings2012

    • Author(s)
      Nishimura M, Nishie W, et al.
    • Journal Title

      Br J Dermatol

      Volume: 167 Issue: 1 Pages: 221-2

    • DOI

      10.1111/j.1365-2133.2012.10855.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Pathogenesis of bullous pemphigoid.2015

    • Author(s)
      Nishie W.
    • Organizer
      Inauguration Symposium Inflammatory Skin Diseases
    • Place of Presentation
      Lubeck University, Lubeck, Germany
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 全長XVII型コラーゲンを抗原としたELISAによる粘膜類天疱瘡患者自己抗体の検出2015

    • Author(s)
      泉 健太郎、西江 渉、夏賀 健、岩田浩明、氏家英之、清水 宏
    • Organizer
      第37回水疱症研究会
    • Place of Presentation
      コラッセ福島、福島市
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Context-dependent tight regulation of collagen XVII ectodomain shedding in skin.2014

    • Author(s)
      Nishie W, Natsuga K, Izumi K, Ujiie H, Hata H, Nakamura H, Shimizu H
    • Organizer
      The 39th Annual Meeting of the Japanese Society of Invesitigative Dermatology
    • Place of Presentation
      ホテル阪急エキスポパーク(吹田市)
    • Year and Date
      2014-12-12 – 2014-12-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] Shedding of the type VII collagen2013

    • Author(s)
      Nishie W
    • Organizer
      International Pre IID 2013 Meeting on Autoimmune Bullous Diseases
    • Place of Presentation
      Luebeck University (Luebeck, Germany)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Detection of pathological cleavage sites and neoepitopes on collagen XVII, a major autoantigen for bullous pemphigoid.2013

    • Author(s)
      Nishie W, Ujiie H, Izumi K, Shimizu H
    • Organizer
      International Investigative Dermatology 2013
    • Place of Presentation
      Edinburgh International Conference Centre (Edinburgh, Scotland)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Neoepitopes on the modified amino-terminus of the shed ectodomain of collagen XVII2012

    • Author(s)
      Nishie w, Ujiie H, et al.
    • Organizer
      The 43rd Annual Meeting of the European Society for Dermatological Research
    • Place of Presentation
      Venice Lido Congress Centre, Venice, Italy
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi