| Project/Area Number |
12470053
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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 |
Experimental pathology
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
SASAHARA Masakiyo Toyania Medical and Pharmaceutical University, Faculty of Medicine, Professor, 医学部, 教授 (20154015)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Yoko Toyania Medical and Pharmaceutical University, Faculty of Medicine, Instructor, 医学部, 助手 (00361949)
OYA Takeshi Toyania Medical and Pharmaceutical University, Faculty of Medicine, Instructor, 医学部, 助手 (00343179)
FUJIMORI Toshihiko Kyoto Post-graduate school, Faculty of Medicine, Instructor, 医学研究科, 助手 (80301274)
川口 誠 富山医科薬科大学, 医学部, 助手 (50204699)
石澤 伸 富山医科薬科大学, 附属病院, 助手 (40222989)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | platelet-derived growth factor / knockout mouse / brain / development / FGF / Klotho / ZFH transcription factor / kidney / マウス / apoptosis / 再生 / 受容体 / conditional knockout / 高次脳機能 / 神経伝達 / Conditional knockout / 脳 / ノックアウト |
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| Research Abstract |
1)Establishment of the model animal.
We have found that the CNS is one of the organs that express platelet-derived growth factor(PDGF) and its receptors at high levels. However, their function still remains undetermined in CNS in vivo. To understand the function, we established conditional knockout mouse of PDGF beta-receptor(PDGFR-b) using Cre-loxP system in this project. Mice with foxed PDGFR-b allele do not show apparent abnormality. Now study is under process on the mice in which PDGFR-b is conditionally ablated only in CNS by the crossbreeding with Cre transgenic mice. These mice survive and grow up until adult, indicating that the model established in current study is useful for the functional study of PDGFR-b.
2)Other studies
In neonatal rat, we found that the PDGF-B chain expressed in CNS is important physiological modulator of the vulnerability of brain to excitotoxicity, which vulnerability is specific to neonatal period in both rodent and human. It was suggested that the enforcement of PDGF-B/PDGFR-b could protect the immature brain at risk of hypoxic and ischemic injury.
We demonstrated that PDGF-B expression was induced in the process of sciatic nerve regeneration after crush injury. Furthermore, the active form of Src, a signaling molecule at the downstream of PDGFR, is also induced at the same time. Separately, we showed that the PDGF-B induced tubular epithelial cell regeneration via the activation of Src after ischemic insult of kidney. These findings obtained indicate that induction of PDGF-B signaling is important for the regeneration of nerve and kidney.
We conducted studies on basic aspects of brain development focusing on the expression of ZFH transcription factors. Also we studied on FGF, Klotho gene.
In summary, we established mouse model to study the function of PDGF based on Cre/loxP system. We are starting to obtain data indicating the significance of PDGF in CNS. Further study would be required.
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