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1997 Fiscal Year Final Research Report Summary

DEVELOPMENT AND ANALYSIS OF A MODEL MOUSE FOR NONKETOTIC HYPERGLYCINEMIA

Research Project

Project/Area Number 08672593
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

KURE Shigeo  TOHOKU UNIVERSITY,SCHOOL OF MEDICINE,RESEARCH ASSOCIATE, 医学部, 助手 (10205221)

Co-Investigator(Kenkyū-buntansha) TOMINAGARA Teiji  TOHOKU UNIVERSITY,SCHOOL OF MEDICINE,RESEARCH ASSOCIATE, 医学部, 助手 (00217548)
Project Period (FY) 1996 – 1997
Keywordsglycine metabolism / ES cells / transgenic mouse / chromosomal location / CA repeat marker
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.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Takeuchi, K, Kure, S. et al.: "Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelmen's syndrome." J.Clin.Endocrin.Metab.81. 4496-4499 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwama, H, K, Kure, S. et al.: "Depletion of cerebral D-serine in non-ketotic hyperglycinemia:possible involvement of glycine cleavage system in control of endogenous D-scrine." Biochem.Biophys.Res.Commun.231. 793-796 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kure, S. et al.: "Nonketotic hyperglycinemia:Biochemical,molecular,and neurological aspect." Jpn.J.Hum.Genet.42. 13-22 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda, H.Kure, S. et al.: "Molecular analysis of dihydropteridine reductase deficiency:Identification of two novel mutations in Japanese patients." Human Genetics. 100. 637-642 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kure, S. et al.: "Dinucleotide repeat polymorphism in 65K-glutamate decarboxylase gene." Jpn.J.Hum.Genet.42. 429-431 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wataya, K, Kure, S. et al.: "Two CRT2 mutations in three Japanese patients with carnitine palmitoyltransferase II deficiency:functional analysis and asociation with polymorphic haplotypes and two clinical phenotypes." Human Mutation. in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kure, S. et al.: "A missense mutation(His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia." Human Genetics. in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kure, S. et al.: "Mutation and polymorphic marker analtes of 65k- and 67k-glutamate decarboxylase genes in two families with pyridoxine-dependent epilepsy" Journal of Human Genetics. in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kure, S. et al.: "A subtype of pyridoxine dependent epilepsy with normal CSF glutamate concentration." J.Inher.Metabol.Dis.in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kure, S. et al.: "A one-base deletion and a missense mutation(D276H) in the T-protein gene from a Japanese family with nonketotic hyperglycinemia." Journal of Human Genetics. in press. (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeuchi, k, Kure, S,et al.: "Association of a mutation in thiazide-sensitive Na-C1 cotrasporer with familial Gitelmen's syndrome." J.Clin.Endocrin.Metab.81. 4496-4499 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwama, H,Kure, S.et al.: "Depletion of cerebral D-serine in non-ketotic hyperglycinemia : possible involment of glycine cleavage system in control of endogenous D-scrine." Biochem.Biophys.Res.Commun.231. 793-796 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kure, S.et al.: "Nonketotic hyperglycinemia : Biochemical, molecular, and neurological aspect." Jpn.J.Hum.Genet.42. 13-22 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda, H.Kure, S.et al.: "Molecular analysis of dihydropteridine reductase deficiency : identification of two novel mutations in Japanese patients." Human Genetics. 100. 637-642 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kure, S.et al.: "Dinucleotide repeat polymorphism in 65K-glutamate decarboxylase gene." Jpn.J.Hum.Genet.42. 429-431 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wataya, K.Kure, S.et al.: "Two CPT2 mutations in three patients with carnitine palmitoyltransferase II deficiency : functional analysis and association with polymorphic haplotypes and two clinical phenotypes." Human Mutation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kure, S.et al.: "A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia." Human Genetics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kure, S.et al.: "Mutation and polymorphic marker analtes of 65K-and 67K-glutamate decarboxylase genes in two families with pyridoxine-dependent epilepsy." Journal of Human Genetics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kure, S.et al.: "A subtype of pyridoxine dependent epilepsy with normal CSF glutamate concentration." J.Inher.Metabol.dis.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kure, S.et al.: "A one-base deletion (183delC) and a missense mutation (D276H) in the T-protein gene from a Japanese family with nonketotic hyperglycinemia." Journal of Human Genetics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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