Project/Area Number |
10680717
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
|
Research Institution | Osaka University |
Principal Investigator |
FUNAKOSHI Hiroshi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40273685)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Toshikazu Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00049397)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | Hepatocyte growth factor / HGF / c-Met / HLP / neurotrophic factor / neuron / Transgenic mice / neurodegenerative disease / クローニング / トランスジェニック / Sky / Gas6 / チロシンキナーゼ型受容体 |
Research Abstract |
(1) Expressional analysis of HGF and c-Met/HGF receptor in the nervous system Expression of HGF and c-Met were examined by quantitative competitive RT-PCR and immunohitochemistry. (a) Cerebral cortex development; both HGF and c-Met was regulated in a dynamic fashion. Taken together with in vitro activities of HGF that accelerate survival, neurite, and migration, it is suggested that HGF may have critical role for the cortical layer formation. (b) Retinal development; both c-Met and HGF were expressed in retinal cells during development. Especially c-Met expression and in retinal neurons after eye opening and adult photoreceptor cells in adult, suggesting the activity dependent role of HGF in retina. (2) Neurotrophic activities of HGF in vitro. Neurotrophic activities, such as survival, neurite extension, proliferation in early neuroepithelial cells and migration promoting activities in different types of neural cells were examined. (3) Identification of HGF-like protein (HLP) as a novel neurotrophic factor. We first identify HLP as a neurotrophic factor using chicken peripheral ganglion cells. (4) Role of HGF on motor neurodegenerative disease using transgenic approach (a) Generation of HGF-overexpressing transgenic mice (NS-HGF-Tg) under the control of neuronal specific promoter. Generated mice were characterized. (b) Generation and characterization of double-transgenic mice of HGF-ALS-transgenic mice. By mating HS-HGF-Tg with ALS-transgenic mice, comparing with double-transgenic mice, single-transgenic mice or sister wild-type mice.
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