1994 Fiscal Year Final Research Report Summary
Development of high-level expression vectors in embryonic and hematopoietic stem cells and generati of GM-CSF and IL-3 of receptor transgenic mice
| Project/Area Number |
04559003
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
広領域
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ARAI Ken-ichi Institute of Medical Science, The Univ.of Tokyo, Professor, 医科学研究所, 教授 (00012782)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Tohru School of Medicine, Yokohama City Univ.Associate Professor, 医学部, 助教授 (50100110)
TOYOTA Yutaka Institute of Medical Science, The Univ.of Tokyo, Professor, 医科学研究所, 教授 (90050418)
MASAI Hisao Institute of Medical Science, The Univ.of Tokyo, Assistant Professor, 医科学研究所, 助手 (40229349)
YOKOTA Takashi Institute of Medical Science, The Univ.of Tokyo, Associate Professor, 医科学研究所, 助教授 (50134622)
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| Project Period (FY) |
1992 – 1994
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| Keywords | GM-CSF receptor / Cytokine receptor / receptor expression / signal transduction / transgenic mice / hematopoietic cell / differentiation / proliferation |
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| Research Abstract |
Transgenic mice expressing the human GM-CSF (hGM-CSF) high affinity receptor were generated. Expression of the receptor is under control of the H-2L^d class I promoter, resulting in its expression on numerous hematopoietic cells, including splenocytes, thymocytes, and bone marrow cells. Murine GM-CSF (mGM-CSF) does not bind to the human receptor, therefore hGM-CSF receptor(hGMR)transgenic mice display normal phenotypes in the absence of exogenous hGM-CSF.In methylcellulose colony assays which examine bone marrow hematopoietic progenitors from hGMR transgenic mice, addition of hGM-CSF lead to the formation of multiple lineage colonies, including erythrocyte colonies whose genration normally depends on erythropoietin. In the presence of mGM-CSF,only granulocyte and macrophage colonies were generated. These data suggest that cytokine responsiveness of various myeloid progenitors is regulated at the level of receptor expression rather than through downstream signal transduction machinery. We also examined effects of hGM-CSF signalling on the differentiation of thymocytes from hGMR transgenic mice. hGM-CSF can transduce proliferation signals to thymic subsets when they express hGMR,while thymocytes does not respond to mGM-CSF.Addition of hGM-CSF to fetal thymic organ cultures inhibited thymocyte differentiation in stage-specific manner. In vivo administration of hGM-CSF into hGMR mice also showed that hGM-CSF supports myeloid lineage cell proliferation and differentiation but inhibits thymocyte differentiation.
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