2006 Fiscal Year Final Research Report Summary
Functional and therapeutic study on inhibitory genes associated with collagen diseases
| 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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| 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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[Journal Article] Cappuccino mutation in an autoimmune-prone strain of mice suggested a role of platelet function in the progression of immune-complex crescentic glomerulonephritis.2006
Author(s)
Yoshida M, Saiga K, Hato T, Iwaki S, Niiya T, Arita N, Komori H, Tsubaki T, Furukawa H, Terada M, Maeyama K, Nemoto K, Nose M, Ono M.
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Journal Title
Arthritis Rheum 54
Pages: 2934-43
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] NK026680, a novel suppressant of dendritic cell function, prevents the development of rapidly progressive glomerulonephritis and perinuclear anti-neutrophil cytoplasmic antibody (pANCA) in SCG/Kj mice.2006
Author(s)
Saiga K, Tokunaka K, Ichimura E, Toyoda E, Abe F, Yoshida M, Furukawa H, Nose M, Ono M.
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Journal Title
Arthritis Rheum 54
Pages: 3707-3715
Description
「研究成果報告書概要(欧文)」より
