| Project/Area Number |
08672593
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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 |
Human genetics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
KURE Shigeo TOHOKU UNIVERSITY,SCHOOL OF MEDICINE,RESEARCH ASSOCIATE, 医学部, 助手 (10205221)
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| Co-Investigator(Kenkyū-buntansha) |
TOMINAGARA Teiji TOHOKU UNIVERSITY,SCHOOL OF MEDICINE,RESEARCH ASSOCIATE, 医学部, 助手 (00217548)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | glycine metabolism / ES cells / transgenic mouse / chromosomal location / CA repeat marker / 非ケトーシス型高グリシン血症 / ノックアウトマウス / NMDA受容体 / in sity hybridization / 相同組み換え |
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| Research Abstract |
Nonketotic hyperglycinemia (NKH) is an inherited metabolic disease, characterized by marked elevation of the glycine level in body fluid and severe neurological abnormalities. NKH is caused by defect in the mitochondrial glycine cleavage system (GCS). The GCS consists of the four protein components referred to as P-, T-, H-, and L-proteins. In the central nervus system (CNS) the overall activity of the GCS was high in forebrain and cerebellum, whereas it was hardly detected in spinal cord and brain stem. In line with this observation the glycine content was high in spinal cord and cerebrum, but low in cerebral cortex and cerebellum. To elucidate the molecular pathogenesis of NKH we examines the GCS in mouse brain by using a transgenic technique. We mapped mouse P-protein gene was on chromosome 19C and isolated a intragenic CA repeat marker. We generated a transgenic (Tg) mouse overxpressing the human P-protein cDNA which was under control of potent CAG promoter. The Tg mouse expressed a large amount of human P-protein mRNA and the overall GCS activities in various regions of mouse brain. The glycine content in the spinal cord of the Tg mouse was markedly reduced compared with wild type mouse. These data suggested that the overall activities of the GCS in each region of CNS was closely correlated with the expression level of the P-protein, and the GCS plays a pivotal role in regulation of the glycine content in various regions of CNS.
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