1997 Fiscal Year Final Research Report Summary
Analysis of functions and differentiation of mast cells
| Project/Area Number |
08044275
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
NAKANO Touru Osaka University BIKEN,DMCB,Professor, 微生物病研究所, 教授 (00172370)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Koichiro Osaka University BIKEN,DMCB,Research Associate, 微生物病研究所, 助手 (90294123)
TAKAHASHI Tomomi Osaka University BIKEN,DMCB,Research Associate, 微生物病研究所, 助手 (70283801)
ギャリ スティーブ ハーバード大学, 医学部・病理学, 教授
グラフ トーマス ヨーロッパ分子生物学研究所, 細胞分化部門, 教授
GRAF Thomas EMBL,Cell Regulation, Professor
GALLI Stephen J Harvard Med Sch, Dept.Pathol.Professor
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| Project Period (FY) |
1996 – 1997
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| Keywords | mast cell / cell differentiation / transcription factor / gene targeting |
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| Research Abstract |
In order to analyze the molecular mechanisms of mast cell differentiation and the functions of the maste cells, following experiments were carried out by using in vitro hematopoietic differentiation method (OP9 system) which we recently developed.
One of the collaborators, Prof.Stephen J.Galli of Harvard Medical School constructed a targeting vector for disrupting the gene which is expressed at the activation of mast cells and presumably play important roles in the function of mast cells. ES (embryonic stem cell) lines in which the gene is disrupted are being produced. After establishing the cell line(s), in vitro differentiation from the cell lines to mast cells will be carried out and the function of the mast cells obtained by the differentiation induction will be done. At the same time, establishment of the ES cell lines which constitutively express the gene was attempted. However, expression of the genes decreased drastically during the differentiation induction into mast cells. To overcome this problem, Nakano and Takahashi of Osaka University screened some promoters suitable for this experiment. Finally a couple of good promoters were found.
In collaboration with Prof. Thomas Graf of EMBL,several expression plasmids were constructed to analyze the effects of c-myb on the differentiation of mast cells. And the plasmid whose activity can be conditionally controlled is already obtained. After expressing these genes in ES cells and the differentiation induction will be carried out. It will be examined soon what kind of effects loss of function and gain of function of c-myb would have.
c-myb and GATA-1, both of which are considered to have crucial roles during the mast cell differentiation, interact each other by utilizing a transcriptional co-activator, CBP which function as a coactivator of various transcription factors.
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[Publications] J.L.de la Pompa, A.Wakeham, K.M.Correia, E.Samper, S.Brown, R.J.Aguilera, T.Nakano, T.Honjo, T.W.Mak, J.Rossant, R.A.Conlon.: "Consevation of the Notch signalling pathway in mammalian neurogenesis." Development. 124. 1139-1148 (1997)
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