| Project/Area Number |
09470229
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Mie University |
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Principal Investigator |
SHIKU Hiroshi Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80154194)
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| Co-Investigator(Kenkyū-buntansha) |
KATAYAMA Naoyuki Mie University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (20185812)
NISHIKAWA Masakatsu Mie University, Hospital, Lecturer, 医学部・附属病院, 講師 (30144257)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | metastasis suppression gene / nm23 / NDP kinase / hematopoietic differentiations / transgenic mouse / knockout mouse / dendritic cells / nm23NDP Kinase / IL6 / NM23 / 転移抑制遺伝子 / transgenic マウス / 造血細胞 |
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| Research Abstract |
1) We produced transgenic mice human nm23/NDP kinase genes, nm23-H1 or -H2. Expression of both nm23 isotypes was confirmed by isotopes specific monoclonal antibodies we produced. Several different lines of transgenic mice with different level of isotype expression were obtained. While we observed those transgenic mice for about two years, no different of delivery, growth and behavior between transgenic mice and wild type mice was observed. No pathological change was observed, either.
2) We produced nm23M2 gene-, one of two murine nm23/NDP kinase isotypes, knockout mice. Expression of nm23M2 was completely lost by examining them with nm23M2 protein specific monoclonal antibodies we produced. No difference of delivery, growth and behavior between nm23M2 knockout mice and wild type mice was observed during about 2 years observation. No pathological change was observed, either.
3) In hematological stem cell colony assay of normal mice, addition of human or murine nm23 fusion protein with GST did not give any influence for colony formation of stem cells.
4) As a part of analyses of human hematopoietic stem cell differentiation, a system to observe differentiation of CD14ィイD1+ィエD1 monocytes to either dendritic cells or macrophages was established. The requirement of cytokines for cellular differentiation was examined. Among several cytokines examined, presence of IL6 inhibited monocyte differentiation to dendritic cells and promoted their differentiation to macrophages. Relevance of nm23/NDP kinase in these differentiation pathway is now under investigation.
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