| Project/Area Number |
18390309
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Hirosaki University |
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Principal Investigator |
SAWAMURA Daisuke Hirosaki University, Hirosaki University, Graduate of Medicine, Professor (60196334)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Hiroshi Hokkaido University, Graduate of Medicine, Professor (00146672)
SHIMIZU Tadamichi Toyama University, Faculty of Medicine, Professor (70260396)
NISHIMURA Emi Kanazawa University, Faculty of Cancer, Professor (70396331)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,730,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2006: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | pemphigoid / knockout mouse / transgenic mouse / epitope / decoy / BP180 / typeXVII collagen / gene therapy / 水疱性天疱瘡 |
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| Research Abstract |
Bullous pemphigoid (BP) is an autoimmune skin disease characterized by painful erosions and blisters arising on the skin and mucous membrane, and demonstrates distinctive subepidermal clefting histologically. The patients have lgG autoantibody that reacts 180-kD BP antigens in basement membrane zone. Previous passive transfer experiments with lgG from BP patients into animals fails reproducing disease due to the epitope differences between human and recipients. To overcome the species difference between autoantibody and autoantigen, we developed novel approach. We first generated knockout mouse of the BP180 gene, which revealed blister formation as found in human ortholog knockout, non-Herliz junctional epidermolysis bullosa (EB). Next, transgenic rescue experiment using human BP180 cDNA transgene was performed, which resulted in correction of abnormal phenotypes of the knockout mice. Successful transgenic rescue of BP180 KO mice also provides a great promise to gene therapy of EB. These rescued mice with humanized BP180 succeeded in blister formation when lgG from BP patients were passively transferred. Furthermore, treatment with 70 mer recombinant antigenic peptide prevented blister formation significantly. This study first demonstrated direct evidence of BP antibody pathogenicity and feasibility of epitope decoy therapy in BP, and also showed promising effectiveness of corrective gene therapy of EB.
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