Generation of a disease model for epidermolysis bullosa acquisita using autoantigen-humanized mice and application for the development of novel treatment
| Project/Area Number |
20591312
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Hokkaido University |
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Principal Investigator |
SHIBAKI Akihiko Hokkaido University, 大学院・医学研究科, 非常勤講師 (40291231)
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| 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)
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| 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)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(22 results)
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[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.
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Journal Title
American Journal of Pathology 176
Pages: 914-25
Related Report
Peer Reviewed
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[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.
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Journal Title
Journal of Immunology 184
Pages: 2166-74
Related Report
Peer Reviewed
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[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.
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Journal Title
Journal of Immunology 185
Pages: 7746-55
Related Report
Peer Reviewed
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[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.
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Journal Title
Journal of Investigative Dermatology 129
Pages: 2288-95
Related Report
Peer Reviewed
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[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.
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Journal Title
American Journal of Pathology 175
Pages: 2508-17
Related Report
Peer Reviewed
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