| Project/Area Number |
11357003
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Experimental pathology
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
SHIRAI Toshikazu Department of Pathology, Juntendo University School of Medicine, Professer, 医学部, 教授 (30115860)
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| Co-Investigator(Kenkyū-buntansha) |
HAMANO Yoshitomo Department of Pathology, Juntendo University School of Medicine, Instructor, 医学部, 助手 (10281354)
JIANG Yi Department of Pathology, Juntendo University School of Medicine, Instructor, 医学部, 助手 (50276466)
HIROSE Sachiko Department of Pathology, Juntendo University School of Medicine, Assiclate Professer, 医学部, 助教授 (00127127)
NISHIMURA Hiroyuki Department of Biomedical Enginee, Toin Human Science and Technolog Center, Toin University of Yokoh, Professor, 工学部, 教授 (60189313)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥24,400,000 (Direct Cost: ¥22,300,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2001: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | Autoimmunity / Genetics / Genome / Genome screening / Microsatellite / Multigeneic disease / SLE / Susceptibility genes / B細胞活性化 / Fe受容体IIB遺伝子 / IgG遺伝子制御領域多型 / 自己免疫疾患 / 高IgG抗体応答 / 疾患感受性遺伝子 / 抗リン脂質抗体症候群 / 高IgG血症 / IgFc受容体IIB遺伝子 / 遺伝子統御領域多型 / 組織プラスミノーゲンアクチベーター遺伝子 |
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| Research Abstract |
Systemic lupus erythematosus (SLE) is a complex, multigenic autoimmune disease with a wide spectrum of clinical manifestations. Much of the pathology is attributed to deposition to various tissues of immune complexes continuously formed with autoantibodies ; thus, the pathogenesis is related to genetic dysregulation of self-reactive B cells. However. as the complexity of polygenic inheritance of SLE phenotypes is considerable, susceptibility loci and genes have not been identified precisely. To solve some such difficulties, we designed genetic studies on SLE using murine lupus models. Major difficulties were related to the fact that each specific aspect of diverse SLE phenotypes(clinical manifestations and immunological abnormalities)is mostly controlled separately by a different set of susceptibility loci. Involvement of positive and negative epistatic gene interactions often puzzles genetic analyses of SLE phenotypes. Studies on genetic regulations of emergence, clonal expansion, differentiation and maturation of self-reactive B cells showed that they are regulated at different stages by different of SLE-susceptibility. There were several positional candidate polymorphic genes that were potentially responsible for the abnormal B cell phenotypes. Further studies on the identification of susceptibility genes and their functions are ongoing using genetically manipulated and recombinant mice. Such knowledge will lead to elucidation of genetic and cellular mechanisms involved in dysregulation of self-reactive lymphocytes in the pathogenesis of SLE.
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