2003 Fiscal Year Final Research Report Summary
Functional analysis of mouse 3-phosphoglycerate dehydrogenase (Phgdh) gene by using gene targeting
| Project/Area Number |
14580756
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
FURUYA Shigeki RIKEN (The Institute of Physical and Chemical Research), Neuronal Circuit Mechanisms Research Group, Research Scientist, 神経回路メカニズム研究グループ, 研究員 (00222274)
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| Project Period (FY) |
2002 – 2003
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| Keywords | serine / glia / amino acid / neural stem cells / knockout mouse / metabolic defect / brain development / embryonic lethality |
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| Research Abstract |
D-3-Phosphoglycerate dehydrogenase (Phgdh ; EC 1.1.1.95) is the first committed enzyme of L-serine biosynthesis in the phosphorylated pathway. To determine the physiological importance of Phgdh-dependent L-serine biosynthesis in vivo, we generated Phgdh-deficient mice using targeted gene disruption in embryonic stein cells. The absence of Phgdh led to a drastic reduction of L-serine metabolites such as phosphatidyl-L-serine (PS) and sphingolipids. Phgdh null embryos have small bodies with abnormalities in selected tissues and died after days post-coitum 13.5. Striking abnormalities were evident in the central nervous system in which the Phgdh null mutation culminated in hypoplasia of the telencephalon, diencephalon, and mesencephalon ; in particular, the olfactory bulbs, ganglionic eminence, and, cerebellum appeared as indistinct structures. These observations demonstrate that the Phgdh-dependent phosphorylated pathway is essential for normal embryonic development, especially for brain morphogenesis.
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Research Products
(13 results)
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[Publications] Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., et al.: "Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neuro-developmental defects and results in embryonic lethality."J.Biol.Chem.. 279. 3573-3577 (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Shimizu, M., Furuya, S., Shinoda, Y., Mitoma, J., Okamura, T., Miyoshi, I., et al.: "Functional analysis of mouse 3-phosphoglycerate dehydrogenase (Phgdh) gene promoter in developing brain."J.Neurosci.Res.. 76. 623-632 (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Mitoma, J., Furuya, S., Shimizu, M., Shinoda, Y., Yoshida, K., Azuma, N., Tanaka, H., et al.: "Mouse 3-phosphoglycerate dehydrogenase gene : Genomic organization, chromosomal localization, and promoter analysis."Gene. (印刷中). (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Chen P., Peng, C., Luff, J., Spring, K., Watters, D., Bottle, S., Furuya, S., Lavin, M.F.: "Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from Atm mutant mice."J.Neurosci.. 23. 11453-11460 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., Tanaka, H., Hashikawa, T., Itohara, S., Hirabayashi, Y.: "Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neuro-developmental defects and, results in embryonic lethality."J.Biol.Chem.. 279. 3573-3577 (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shimizu, M., Furuya, S., Shinoda, Y., Mitoma, J., Okamura, T., Miyoshi, I., Kasai, N., Hirabayashi, Y., Suzuki, Y.: "Functional analysis of mouse 3-phosphoglycerate dehydrogenase (Phgdh) gene promoter in developing brain."J.Neurosci.Res.. 76. 623-632 (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Mitoma, J., Furuya, S., Shimizu, M., Shinoda, Y., Yoshida, K., Azuma, N., Tanaka, H., Suzuki, Y., Hirabayashi, Y.: "Mouse 3-phosphoglycerate dehydrogenase gene : Genomic organization, chromosomal localization, and promoter analysis."Gene. (in press). (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Chen, Peng, C., Luff, J., Spring, K., Watters, D., Bottle, S., Furuya, S., Lavin, M.F.: "Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from Atm mutant mice."J.Neurosci.. 23. 11453-11460 (2003)
Description
「研究成果報告書概要(欧文)」より
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