| 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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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | serine / glia / amino acid / neural stem cells / knockout mouse / metabolic defect / brain development / embryonic lethality / 神経栄養因子 / 細胞増殖 / 脳皮質形成 / 脳 / グリア細胞 / アストロサイト |
|---|
| 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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