Functional and therapeutic study on inhibitory genes associated with collagen diseases

点击翻译按钮获取中文摘要

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