| Project/Area Number |
18500245
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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 |
Neuroscience in general
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
IMURA Tetsuya Kyoto Prefectural University of Medicine, Graduate school of medical science, Assistant Professor (00405276)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | stem cells / neurogenesis / adult brain plasticity / tumor suppressor gene / genetically modified animals / 再生医学 / 脳・神経 / 神経科学 |
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| Research Abstract |
The tumor suppressor Adenomatous Polyposis Coli (APC) is the causative molecule for familial adenomatous polyposis. APC is highly expressed in the adult brains, but its function remains largely unknown. To investigate the roles of APC in the biology of adult neural stem cells, we applied Cre/loxP technology to develop a new mouse model in which APC is knocked out from GFAP-expressing neural stem cells. APC was highly expressed in the adult neurogenic regions such as the subventricular zone-olfactory bulb and the hippocampal dentate gyrus of wild-type mice and its expression was effectively deleted in APC conditional knockout (CKO) mice. Beta catenin, a target of APC-mediated degradation, markedly accumulated in the neurogenic regions. In contrast, beta catenin accumulation was inapparent in astrocytes in which APC was deleted as well. Thus, the effect of APC deficiency on the amount of beta catenin is likely to be cell-type dependent. Although it is generally assumed that beta catenin accumulation induces cell proliferation, cell genesis was moderately reduced in the adult neurogenic regions of APC CKO mice. Furthermore, newly generated cells failed to diffarentiate/mature into new neurons and remained in an immature state, resulting in the severe reduction of adult neurogenesis. APC CKO mice also exhibited the obvious phenotype outside the central nervous system including gut and eye, indicating the importance of APC in the development and maintenance of these organs. Togethet these results show that APC plays an essential role in adult neurogenesis by regulating neuronal diffirentiation/maturation.
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