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Alteration in neural function by an inducible knock-out of tyrosine hydroxylase.

Research Project

Project/Area Number 11680795
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionFujita Health University

Principal Investigator

ICHINOSE Hiroshi  Fujita Health University, Institute for Comprehensive Medical Science, Professor, 総合医科学研究所, 教授 (90192492)

Co-Investigator(Kenkyū-buntansha) OHYE Tamae  Fujita Health University, Institute for Comprehensive Medical Science, Research Associate, 総合医科学研究所, 助手 (10247661)
INAGAKI Hidehito  Fujita Health University, Institute for Comprehensive Medical Science, Research Associate, 総合医科学研究所, 助手 (70308849)
SUZUKI Takahiro  Fujita Health University, Institute for Comprehensive Medical Science, Research Associate, 総合医科学研究所, 助手 (70298545)
ICHINOSE Chiho  Fujita Health University, School of Medicine, Assistant Professor, 医学部, 講師 (10247653)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordstyrosine hydroxylase / catecholamine / dopaminergic neuron / Cre-ERT / Cre-loxP / 相同組み換え / 条件付き遺伝子破壊
Research Abstract

In this project, we plan to knock-out tyrosine hydroxylase at the desired time at the specific organ using the inducible knockout system with Cre-ERT.We constructed a floxed gene in which a crucial exon of thetyrosine hydroxylase gene was flanked by two loxP sites. We are transfecting the gene into ES cells to obtain homologously recombinant clones. We succeeded to obtain homologous recombinants of ES cells, to make chireric mice with the clones, and to produce floxed mice, which have two loxP sequences surrounding exons of tyrosine hydroxylase gene.
For the expression of the inducible recombinase Cre-ERT in dopaminergic neurons, a knock-in mouse line has been generated by introducing (via homologous recombination) Cre-ERT within the first exon of the tyrosine hydroxylase gene. Since tyrosine hydroxylase is a catecholamine-synthesizing enzyme, we expect that the mice specifically express Cre-ERT in tyrosine hydroxylase positive neurons. The mice were successfully created, and we are examining the expression of Cre-ERT by RT-PCR and Western blotting. We will cross the floxed mouse with mouse expressing Cre-ERT in catecholaminergic neurons, and examine the effect of inducible knock-out of the tyrosine hydroxylase gene.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Nagatsu,T.and Ichinose,H.: "Molecular biology of catecholamine-related enzymes in relation to Parkinson's disease."Cell.Mol.Neurobiol.. 19. 57-66 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu,T.and Ichinose,H.: "Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin."Mol.Neurobiol.. 19. 79-96 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichinose,H.: "Molecular cloning of the human Nurrl gene : Characterization of the human gene and cDNAs."Gene. 230. 233-239 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T. et al.: "Neopterin and cuytokines in hereditary dystonia and Parkinson's disease."Pteridines. 10. 5-13 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimoto K. et al.: "Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase."Biochim.Biophys.Acta. 1431. 306-314 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M. et al.: "Increase in level of tumor necrosis factor (TNF)-α in 6-hydroxydopamine-lesioned striatum in rats without influence of systemic L-DOPA on the TNF-α induction."Neurosci.Lett.. 268. 101-104 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inagaki H. et al.: "Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one allele in hereditary progressive dystonia with marked diurnal fluctuation."Biochem.Biophys.Res.Commun.. 260. 747-751 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu I. et al.: "Specific localization of the guanosine triphosphate (GTP) cyclohydrolase-I immunolocalization in the human brain."J.Neural Transm.. 106. 607-617 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M. et al.: "Brain derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson's disease."Neurosci.Lett.. 270. 45-48 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T. et al.: "Cytokines in Parkinson's disease."Neuroscience News. 2. 88-90 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki T. et al.: "Characterization of wild-type and mutants of recombinant human GTP cyclohydrolase I : Relationship to etiology of dopa-responsive dystonia."J.Neurochem.. 73. 2510-2516 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichinose H. et al.: "Molecular genetics of dopa-responsive dystonia."Biol.Chem.. 380. 1355-1364 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Itagaki C. et al.: "Stimulus-coupled interaction of tyrosine hydroxylase with 14-3-3proteins."Biochemistry. 38・47. 15673-15680 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M. et al.: "Caspase activities and tumor necrosis factor receptor R1(p55)level are elevated in the substantia nigra from Parkinsonian brain."J.Neural Transm.. 107. 335-341 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hibiya M. et al.: "Normal values and age-dependent changes in GTP cyclohydrolase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromatography."J.Chromatogr.B.. 740. 35-42 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneko S. et al.: "Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function."Science. 289. 633-637 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shen Y. et al.: "Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson's disease."Human Gene Therapy. 11. 1509-1519 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M. et al.: "Increase in level of tumor necrosis factor (TNF)-α in 6hydroxydopaminelesioned striatum in rats is suppressed by immunosuppressant FK506."Neurosci.Lett.. 289. 165-168 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tazawa M. et al.: "GTP cyclohydrolase I from Tetrahymena pyriformis : cloning of cDNA and expression."Comparative Biochemistry and Physiology Part B. 127. 65-73 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichinose H. et al.: "Molecular mechanisms of hereditary progressive dystonia with marked diurnal fluctuation, Segawa's disease."Brain and Development. 22. S107-S110 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T. et al.: "Cytokines in Parkinson's disease."J.Neural Transm.. [Suppl]58. 143-151 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T. et al.: "Changes in cytokines and neurotrophins in Parkinson's disease."J.Neural Transm.. [Suppl]60. 277-290 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T & Ichinose H: "Molecular biology of catecholamine-related enzymes in relation to Parkinson's disease."Cell Mol Neurobiol. 19. 57-66 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T & Ichinose H: "Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin."Mol Neurobiol. 19. 79-96 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichinose H et al: "Molecular cloning of the human Nurr1 gene : Characterization of the human gene and cDNAs."Gene. 230. 233-239 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T: "Neopterin and cytokines in hereditary dystonia and Parkinson's Disease."Pteridines. 10. 5-13 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimoto K: "Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase."Biochim Biophys Acta. 1431. 306-314 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M: "Increase in level of tumor necrosis factor (TNF)-alpha in 6-hydroxydopamine-lesioned striatum in rats without influence of systemic L-DOPA on the TNF-alpha induction."Neurosci Lett. 268. 101-104 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inagaki H: "Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one allele in hereditary progressive dystonia with marked diurnal fluctuation (HPD)."Biochem Biophys Res Commun. 260. 747-751 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu I: "Specific localization of the guanosine triphosphate (GTP) cyclohydrolase I-immunoreactivity in the human brain."J Neural Transm. 106. 607-617 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M: "Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson's disease."Neurosci Lett. 270. 45-48 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T: "Cytokines in Parkinson's disease."NeuroScience News. 2. 88-90 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki T: "Characterization of wild-type and mutants of recombinant human GTP cyclohydrolase I : Relationship to etiology of dopa-responsive dystonia."J Neurochem. 73. 2510-2516 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichinose H: "Molecular genetics of Dopa-responsive dystonia."Biol Chem. 380. 1355-1364 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Itagaki C: "Stimulus-coupled interaction of tyrosine hydroxylase with 14-3-3 proteins."Biochemistry. 38. 15673-15680 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M: "Caspase activities and tumor necrosis factor R1 (p55) level are elevated in the substantia nigra from parkinsonian brain."J Neural Transm. 107. 335-341 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hibiya M: "Normal values and age-dependent changes in GTP cyclohydrolase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromotography."J Chromatogr. 740. 35-42 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneko S: "Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function."Science. 289. 633-637 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shen Y: "Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson's disease."Hum Gene Ther. 11. 1509-1519 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mogi M: "Increase in level of tumor necrosis factor-a in 6-hydroxydopamine-lesioned striatum in rats is suppressed by immunosuppressant FK506."Neurosci Lett. 289. 165-168 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tazawa M: "GTP cyclohydrolase I from Tetrahymena pyriformis : cloning of cDNA and expression."Comp Biochem Physiol B. 127. 65-73 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ichinose H: "Molecular mechanisms of hereditary progressive dystonia with marked diurnal fluctuation, Segawa's disease."Brain Dev. 22. S107-S110 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T: "Cytokines in Parkinson's disease."J Neural Transm [suppl]. 58. 143-151 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagatsu T: "Changes in cytokines and neurotrophins in Parkinson's disease."J Neural Transm [Suppl]. 60. 277-290 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hibiya M. et al.: "Normal values and age-dependent changes in GTP cyclohydrolase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromatography."J.Chromatogr.B.. 740. 35-42 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaneko S. et al.: "Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function."Science. 289. 633-637 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shen Y. et al.: "Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson's disease."Human Gene Therapy. 11. 1509-1519 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mogi M. et al.: "Increase in level of tumor necrosis factor (TNF)-α in 6hydroxydopamine-lesioned striatum in rats is suppressed by immunosuppressant FK506."Neurosci. Lett.. 289. 165-168 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tazawa M. et al.: "GTP cyclohydrolase I from Tetrahymena pyriformis : cloning of cDNA and expression."Comparative Biochemistry and Physiology Part B. 127. 65-73 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ichinose H. et al.: "Molecular mechanisms of hereditary progressive dystonia with marked diurnal fluctuation, Segawa's disease."Brain and Development. 22. S107-S110 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagatsu T. et al.: "Cytokines in Parkinson's disease."J.Neural Transm.. [Suppl]58. 143-151 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagatsu T. et al.: "Changes in cytokines and neurotrophins in Parkinson's disease."J.Neural Transm.. [Suppl]60. 277-290 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ichinose, H. et al.: "Molecular genetics of dopa-responsive dystonia"Biol. Chem.. Vol.380. 1355-1364 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki, T. et al.: "Characterization of wild-type and mutants of recombinant human GTP cyclohydrolase I: relationship to etiology of dopa-responsive dystonia"J. Neurochem.. Vol.73 No6. 2510-2516 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inagaki, H. et al.: "Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one allele in hereditary progressive dystonia with marked diumal fluctuation"Biochem. Biophys. Res. Commun.. Vol.260. 747-751 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ichinose, H. et al.: "Molecular cloning of the human Nurrl gene : characterization of the human gene and cDNAs"Gene. Vol.230. 233-239 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagatsu, T et al.: "Molecular biology of catecholamine-related enzymes in relation to Parkinson's disease"Cellular and Molecular Neurobiology. 19(1). 57-66 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagatsu, T et al.: "Regulation of pteridine-requiring enzymes by the cofactor tetrahydrobiopterin"Molecular Neurobiology. 19. 79-96 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ichinose, H.. et al.: "Quantification of mRNA of Tyrosine Hydroxylase"Humana Press (In press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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