| Project/Area Number |
17209038
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 |
SHIMIZU Hiroshi Hokkaido University, Graduate School of Medicine, Professor (00146672)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAMURA Daisuke Hirosaki University, Graduate School of Medicine, Professor (60196334)
SHIMIZU Tadamichi Toyama University, Graduate school of Medicine and Pharmaceutical Science, professor (70260396)
AKIYAMA Masashi Hokkaido University, Graduate School of Medicine, Associate Professor (60222551)
SHIBAKI Akihiko Hokkaido University, Hospital, Assistant Professor (40291231)
MCMILLAN James Hokkaido University, Creative Research Initiative"Sosei", Professor (30374721)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Fiscal Year 2007: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2006: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2005: ¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
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| Keywords | immunology / animal / cell / tIssue / internal medicine / pathology |
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| Research Abstract |
The aim of this study is to establish an animal model for bullous pemphigoid (BP), investigate the BP pathomechanisms, and develop a novel therapeutic strategy for BP. Production of the anti human type XVII collagen (COLXVII) was induced in the Wild type mice by skin grafting from human COLXVII transgenic mice, which express human COLXVII at epidermal basement membrane zone. Indirect immunofluorescence analysis revealed the production of high titer (more than 1280x) anti human COLXVII antibody detectable at three weeks after the immunization. Western blotting using recombinant human COLXVII protein demonstrated positive signal at 180 kD. Three to four weeks after the immunization with skin grafting, splenocytes were prepared form immunized wild type mice, and transferred into irradiated (4~8.5Gy) COXVV humanized mice, which express human COLXVII, but not mouse COLXVII. High titer anti human COLXVII antibody was detected at 10 days after the transfer, and BP like erythema and erosions were developed on the pri-orbital and peri-oral area. Histopathological analysis demonstrated subepidermal blister formation, and inflammatory cell infiltration at the upper dermis. Direct immunofluorescence analysis showed linear deposition of IgG and C3 at epidermal basement membrane zone. These results indicate that this novel BP animal model is demonstrates clinical, histological and immunopathological features of BP.
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