| Project/Area Number |
12670444
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Toin University of Yokohama |
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Principal Investigator |
NISHIMURA Hiroyuki Professor, Toin Human Science and Technology Center, Toin University of Yokohama, 工学部, 教授 (60189313)
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| Co-Investigator(Kenkyū-buntansha) |
KODERA Yo Associate Professor, Toin University of Yokohama and Technology Center, Toin University of Yokohama, 工学部, 助教授 (80205426)
OZAKI Shoichi Associate Professor, Department of Medicine and Clinical Science, Kyoto University School of Medicine, 医学部, 講師 (00231233)
ISHIKAWA Sho Lecturer, Department of Pathology, Juntendo University School of Medicine, 医学部, 講師 (00276479)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | systemic autoimmune diseases / SLE / New Zealand mice / (NZB x NZW) F1 / NZB mice / NZW mice / CD4+Th cells / CD69 / CD4陽性T細胞 / 自発的活性化 / CD4陽性T細胞サブセット / マイクロサテライトDNA / Quantitative Trait Loci(QTL) / 主要組織適合遺伝子複合体 / リンパ球の活性化 / 連鎖解析 / Quantitative Trait Loci / 自己免疫疾患 / Systemic Lupus Erythematosus / New Zealand系マウス / (NZBxNZW) F1 / (NZB x NZW)F1マウス / Th細胞 / モデルマウス / 多因子病 |
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| Research Abstract |
The F1 hybrid of NZB (New Zealand Black) and NZW (New Zealand White) strains of mice has been studied as a murine model of systemic lupus erythematosus (SLE). In the hybrid mice, B1 (CD5+) cells were shown to be responsible for the autoantibody production. However, expression of SLE phenotypes of these mice is strictly dependent on CD4+ T cells. These mice show an age-dependent spontaneous activation and subset skewing of peripheral CD4+ T cells as reflected by the abnormal cytokine productions, elevated frequency of CD4+ T cells positive for an early activation marker CD69, and decreased frequencies of CD4+ T cells positive for the differentiation markers CD62L and/or NTA260. To study the genetic control of abnormal features of peripheral CD4^+ T cells in the ( NZB x NZW) F1 mice, we conducted genome-wide mapping of the quantitative trait loci (QTL) regulating the frequencies of CD69+CD4+, CD62L+CD4+ and NTA260+CD4+ T cells in the spleens of (NZB x .NZW) F1 x NZW backcross mice. Elevated frequency of CD69+CD4+ T cells, and decreased frequencies of CD62L+CD4+ and NTA260+CD4+ T cells were under the common multigenic control, in which interaction of the heterozygosity of the MHC class II loci and a hitherto unknown locus designated as Sta-1 ( spontaneous T-cell activation ) on chromosome 12 plays a major role. These genetic interactions were distinct from those involved in the abnormal functions of B1 cells. Therefore, in (NZB x NZW) F1 mice, abnormal functions of CD4+ T cells and B1 cells are based on distinct multi-genetic predisposition, both of which contribute to the manifestation of SLE phenotypes of the hybrid mice.
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