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1998 Fiscal Year Final Research Report Summary

Research for brain functions by generating dopamine receptor gene knockout mice

Research Project

Project/Area Number 09480220
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

KATSUKI Motoya  The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (20051732)

Co-Investigator(Kenkyū-buntansha) NAKAO Kazuki  The Institute of Medical Science, The University of Tokyo, Visiting Research Ass, 医科学研究所, 寄付研究部門教員 (20217657)
NAKAMURA Kenji  The Institute of Medical Science, The University of Tokyo, Research Associate, 医科学研究所, 助手 (90253533)
AIBA Atsu  The Institute of Medical Science, The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (20271116)
Project Period (FY) 1997 – 1998
Keywordsanimal models / pharmacology / dopamine receptor / brain function / gene targeting / gene replacement / ES cell / humanized mouse
Research Abstract

It is impossible to use human beings for the experimental studies of brain functions. Thus, we have to develop animal models for human brain functions. In human brain, dopamine is one of the key transmitters in the central nervous systems and is also suggested to control emotion, movement as well as various kinds of behaviors.
To elucidate the dopaminergic systems in the brain, we planned to generate dopamine receptor mutant mice, each of which lacks one of five dopamine (D1R-D5R) receptor genes. D1R, D2R and D4R mutant mouse lines were established by gene targeting and by intercrossing of the heterozygous mice, respectively. D4R and D2R mutant mice were crossed between them and the double mutant mice were obtained. These mice appeared very quiet and relatively smaller than the D2R or D4R mutant mice, probably because of the hortage of the appetite. The obvious abnormal behavior was also observed in these mutant mice.
The D3R and D5R mutant mice have yet to be obtained, though the ES cell lines, each gene of which had been already disrupted and the chimeric mice were also obtained. These mice will be established soon.
We are trying to elucidate the physiological functions of each dopamine receptor by pharmaco-behavioral experiments and by producing double and triple(or more)mutant mice as well.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Sugihara,K., et al.: "Racl is required for the fomation of three germ layers during gastrulation." Oncogene. 17. 3427-3433 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshikawa,H.,et al.: "Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses." Genes to Cells. 3. 685-695 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nomoto,S.,et al.: "The high susceptibility of heterozygous p53(+/-)mice to malformation after foetal irradiation is related to sub-competent apoptosis." Int J Radiat Biol. 785. 245-252 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura,M.,et al.: "Overexpression of a minor component of myelin basic protein isoform(17.2kDa)can restore myeliogenesis in transgenic shiverer mice." Brain Res. 785. 245-252 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakao,K.,et al.: "Production of chimeric mice from cryopreserved blastocysts." J Exp Anim. 47. 167-171 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Honda,H.,et al.: "Cardiovascular anomaly,impaired actin bundling and resistance to Src-induced transformation in mice lacking P130^<Cas>." Nature Genetics. 19. 361-365 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koera,K.,et al.: "K-Ras is essential for the development of the mouse embryo." Oncogene. 15. 1151-1159 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mimura,J.,et al.: "Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in mice lacking the Ah(dioxin)receptor." Gene to Cells. 2. 645-654 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Araki,E.,et al.: "Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy." Biochem Biophys Res Commun. 238. 492-497 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakao,K.,et al.: "Simple and efficient vitrification procedure for cryopreservation of mouse embryos." Exp Anim. 46. 231-234 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukui,Y.,et al.: "Positive and negative CD4+ thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus." Immunity. 6. 401-410 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohmi,K.,et al.: "A novel aortic smooth muscle cell line obtained from p53 knock out mice expresses several differentiation characteristics." Biochem Biophys Res Commun. 238. 154-158 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kameya,S.,et al.: "Dp260 disrupted mice revealed prolonged implicit time of the β-wave in ERG and loss of accumulation of b-dystroglycan in the outer plexiform layer of the retina." Hum Mol Genet. 6. 2195-2203 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibata,H.,et al.: "An oocyte-specific methylation imprint center in the mouse U2afbp-rs/U2af1-rs1 gene marks the establishment of allele-specific methylation during preimplantation" Genomics. 44. 171-178 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugihara, K., et al.: "Rac1 is required for the formation of three germ layers during gastrulation." Oncogene. 17. 3427-3433 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomoto, S., et al.: "The high susceptibility of heterozygous p53 (+/-) mice to malformation after foetal irrasiation isrelated to subcompetent apoptosis." Int J Radiat Biol. 74. 419-429 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshikawa, H., et al.: "Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses." Genes to Cells. 3. 685-695 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, M., et al.: "Overexpression of a minor component of myelin basic protein isoform (17.2kDa) can restore myeliogenesis in transgenic shiverermice" Brain Res. 785. 245-252 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakao, K., et al.: "Production of chimeric mice from cryopreserved blastocysts." J Exp Anim. 47. 167-171 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Honda, H., et al.: "Cardiovascular anomaly, impaired actin bunding and resistance to Src-induced transformation in mice lacking p130Cas." Nature Genetics. 19. 361-365 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koera, K., et al.: "K-Ras is essential for the development of the mouse embryo." Oncogene. 15. 1151-1159 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mimura, J., et al.: "Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor." Gene to Cells. 2. 645-654 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Araki, E., et al.: "Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy." Biochem Biophys Res Commun. 238. 492-497 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakao, K., et al.: "Simple and efficient vitrification procedure for cryopreservation of mouse embryos." Exp Anim. 46. 231-234 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukui, Y., et al.: "Positive and negative CD4+ thymocyte selection by a single NHC class II/peptide ligand affected by its expression level in the thymus." Immunity. 6. 401-410 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohmi, K., et al.: "A novel aortic smooth muscle cell line obtained from p53 knock out mice expresses several differentiation characteristics." Biochem Biophys Res Commun. 238. 154-158 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kameya, S., et al.: "Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of beta-dystroglycan in the outer plexiform layer of the retina." Hum Mol Genet. 6. 2195-2203 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibata, H., et al.: "An oocyte-specific methylation imprint center in the mouse U2afbp-rs/U2af1-rs1gene marks the establishment of allele-specific methylation during preimplanttion developmrnt." Genomics. 44. 171-178 (1997)

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

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Published: 1999-12-08  

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