| Project/Area Number |
17209008
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
KAGEYAMA Ryoichiro Kyoto University, Institute for Virus Research, professor (80224369)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥51,610,000 (Direct Cost: ¥39,700,000、Indirect Cost: ¥11,910,000)
Fiscal Year 2007: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2006: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2005: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
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| Keywords | Nestin-creERT2 mice / floxed Hes1 mice / stem cell / tamoxifen-inducible / conditional knock-out mice / Hes1 oscillation / adult brain / bHLH factor / ニューロン新生 / 側脳室上衣下層 / 海馬歯状回顆粒細胞下層 / tamoxifen誘導性Cre / 成体神経幹細胞 / Hesl / 消化管 / cre-LoxP / Hes / コンディショナル・ノック |
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| Research Abstract |
Neurogenesis usually does not occur in the adult brain, except for the following two regions: the subventricular zone of lateral ventricles and the subgranular zone of the dentate gyrus. The mechanism of maintenance of neural stem cells and the significance of neurogenesis in the adult brain remain to be analyzed. Here, we have produced Nestin-creERT2 mice, which express tamoxifen-inducible cre in neural stem cells, and floxed Hes1 mice, whose Hes1 gene can be deleted by cre. By using these mice, we specifically. deleted Hes genes in the adult brain and found that neurogenesis is blocked in these mutant mice. These results indicate that Hes genes regulate maintenance of neural stem cells in the adult brain as in the embryonic brain. We plan to examine the learning and memory ability of these mice to determine whether neurogenesis is required for such brain functions.
We next found that Hes1 expression dynamically oscillates in the embryonic neural stem cells with a periodicity of about 2-3 hours and that this expression mode is important for proliferation and maintenance of these cells. We also found that Hes1 expression oscillates in the adult neural stem cells, and we plan to examine the significance of Hes1 oscillation in these cells.
To reveal the roles of Hes1 in the adult gastrointestinal tract, we have produced cyp1A1-cre mice. By crossing these mice or villin-cre mice with floxed Hes1 mice, we specifically deleted Hes genes in the adult gastrointestinal tract. We found that in these mice, this organ becomes abnormal, and we plan to examine these defects in more detail.
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