| Project/Area Number |
16390113
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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 |
Experimental pathology
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| Research Institution | Tohoku University |
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Principal Investigator |
ONO Masao Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (20302218)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Naoto Tohoku University, Graduate School of Medicine, Associate professor, 大学院医学系研究科, 助教授 (60291267)
FURUKAWA Hiroshi Tohoku University, Graduate School of Medicine, Research associate, 大学院医学系研究科, 助手 (00372293)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Autoimmune disease / SLE / Animal disease model / SAP / Signal transduction / Adaptor molecule / Autoantibody / Platelet |
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| Research Abstract |
We have identified two mutant genes that individually cure autoimmune diseases in murine models [1,2]. Futhermore, by using two mutant strains of mice with these mutations, we attempted to identify effecter cells and molecules critically involved in the pathogenesis of autoimmune diseases in mouse models, MRL/lpr and EOD. The results provided new understandings as follows :
1.The role of signal lymphocyte activation molecule (SLAM)-associated protein (SAP) in the development, of autoimmunity (Furukawa, Ono, Ishii).
Concanavalin A (ConA)-induced hepatitis, which is known as a model for autoimmune hepatitis, was investigated in wild-type and SAP-deficient strains of mice. The results provided evidences that (1)SAP has a role for suppression of the development of ConA-induced hepatitis, and that (2)the suppressive effect of SAP depends upon a cellular function for hepatic injury, which is independent of Fas ligand (FasL)
2.Characterization of SLAM-family receptors associated With the develop
… More
ment autoimmune diseases in mice (Furukawa, Ono).
We constructed DNA vectors that SLAM-family receptors expressed in vivo and determined an optimal condition of the hydrostatic expression method for each of the expression construct. Effect of induced expression of each SLAM- family receptor in autoimmune mice is on investigation,
3.Identification of platelet function for the development of allergic reaction in mice (Ono).
We established C57BL/6J-cinn/cinn (B6^<cinn>), a congenic strain that shows a defect in platelet functions by a loss-of- function mutation on Cuppuccino gene (Cno). In B6^<cinn> mice significantly higher anaphylactic response to passive IgE challenge (IgE anaphylaxis) was observed than in wild-type mice. The difference was apparent especially in late phase of the reaction. It is indicated that platelet play a role in the recovery from IgE, anaphylaxis.
4.Identifieation of platelet function for the development of experimental and spontaneous arthritis in mice (Ono).
In our preliminary study, B6^<cinn> showed resistant phenotype in collagen-induced arthritis (CIA), suggesting that platelet has a suppressive role in the development of CIA. Less
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