| Project/Area Number |
06454221
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Medical Institute of Bioregulation |
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Principal Investigator |
WATANABE Takeshi Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (40028684)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Daisuke Institute of Life Science, Tokyo Science University, Professor, 生命科学研究所, 教授 (70204914)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1995: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | GeNe-targeting / Signal transduction / Antigen-receptor / Tyrosin kinase / Lyn kinase / HS1 / Apoptosis / Autoimmune disease / シグナル伝達 / 非受容体型チロシンキナーゼ / HS1タンパク / Two-hybrid-system / チロシンリン酸化 / リンパ球分化 / 免疫異常症 |
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| Research Abstract |
In the present study, we established two kinds of gene-targeting mice.one is Lyn^deficient mice and the other, HS1-deficient mice, by applying homologous recomdination. Upon stimulation of cell surface antigen receptors on B cells, two kinds of tyrosine kinases are activated. One is src family tyosine kinasses such as Lyn, Fyn, Lck, Blk and so on. The other is Syk/ZAP70 kinase. In Lyndeficient mice, we found that the responses of the B cells were very low to the stimulation by anti-IgM,CD40 ligand and LPS.In spite of the decreased numbers of mature B cells in the periphery, splenomegaly, lymphadenopathy, hyper IgM syndrome are evident and antoantibodies were produed in Lyn-knockout mice. The mice developed finally autoimmune glomerulonephritis. HS1-deficient mice did not show autoimmune disease but the proliferative responses of B cells and T cells induced by anti-IgM or anti CD3 were impaired. Apoptosis induced by crosslinking of the surface antigen receptors was also impaired.
These results clearly indicate that Lyn-HS1 pathway plays a crucial role in signal transduction pathway from antigen-receptor complex on lymphocyte.
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