2000 Fiscal Year Final Research Report Summary
Immunosuppressive role of TGF-β1 against autoimmune destruction of islet β cells and a basic study on islet β cells of NOD-RGP-TGF-β1 Tg
| Project/Area Number |
11671090
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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 |
Endocrinology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ITAKURA Mitsuo Inst.for Genome Research, Univ.Tokushima professor, ゲノム機能研究センター, 教授 (60134227)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAOKA Takashi Inst.for Genome Research, Univ.Tokushima associate professor, ゲノム機能研究センター, 助教授 (40263826)
YOSHIMOTO Katsuhiko Sch.Med., Univ.Tokushima professor, 医学部, 客員教授 (90201863)
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| Project Period (FY) |
1999 – 2000
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| Keywords | active form TGF-β1 / NOD-RGP-TGF-β1 / autoimmune suppression / glucogon promoter / islet cells / type I diabetes / transplantation / NOD mice |
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| Research Abstract |
Type 1 diabetes is a major public health problem. To determine the immunosuppressive role of TGF-β1 for autoimmune destruction of islet β cells, we used the animal model of NOD-RGP-TGF-β1 transgenic mice(Tg). Qur findings are as follows ;
1)NOD-RGP-TGF-β1(homo)Tg showed impaired glucose tolerance, low serum insulin levels, small islet sizes compared with those of NOD-RGP-TGF-β1(hemi)and littermates. These findings suggest that overexpression of constitutively active TGF-β1 severely impaired the development of islet β cells. It is suggested that a modest TGF-β1 signaling plays an important role for the early stage islet development.
2)To identify the susceptibility genes for diabetes, we performed genome-wide quantitative trait loci(QTL)analysis, using NOD-RGP-TGF-β1 in NOD background which were crossed to C3H genetic background. F2 intercrosses between NOD-RGP-TGF-β1 and C3H strain demonstrated a wide variety of diabetes-related parameters including, plasma insulin concentration, glucose tolerance, and islet morphology. We are performing genome-wide QTL analysis using F2 generation.
3)To determine the immunosuppressive roles of islet β cells in NOD-RGP-TGF-β1(hemi)transgenic mice against autoimmune destrunction, we analysed the model of syngenic islet transplantation to diabetic NOD mice. Immunohistochemical examination of islet cell graft showed the long survival of graft, but syngenic islet cell graft was not protected in diabetic NOD mice. The number of islet cells for trasplantation or other factors have to be examined. We are performing this points.
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