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Production of knockout mice for serine racemase and analysis of the function of D-serine in central nerve system

Research Project

Project/Area Number 17500258
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionDokkyo Medical University

Principal Investigator

KONNO Ryuichi  Dokkyo Medical University, Medicine, Associate Professor, 医学部, 助教授 (30129043)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsSerine racemase / Knockout mouse / D-Serine / NMDA receptor / Schizophrenia / Model mouse / キメラ / ES細胞
Research Abstract

A large amount of D-serine is present in the brains of human and higher animals. D-Serine is considered to bind to N-methy-D-aspartate subtype of glutamate receptors and to stimulate neurotransmission. D-Serine is considered to be converted from L-serine by serine racemase. However, the functions of serine racemase and D-serine are not well understood. Therefore, we have planed to produce serine racemase-knockout mice for the examination of the consequence of the serine racemase deficiency.
In order to produce serine racemase-knockout mice, we screened mouse-genomic library for clones carrying the serine racemase gene and isolated three clones. Upstream and downstream regions of the gene were excised and inserted into the gene-targeting vector containing the neomycin-resistant gene. The constructed targeting vectors were linearized and transfected into mouse embryonic stem (ES) cells. Neomycin-resistant clones were picked up and examined for the homologous recombination with the serine … More racemase gene. The selected ES clones were checked that they retained the normal karyotype. The cells from the three recombinant ES clones were independently inoculated into blastulae from C57BL/6 mice by micromanipulation. The blastulae were inoculated into the uteri of female ICR mice and three chimeric male mice were born. Mating between these chimeric mice and female C57BL/6 mice produced 29 F_1 heterozygotic mice. Brother-sister mating of the F_1 heterozygotic mice produced 65 F_2 mice consisting of 15 serine racemase-deficient homozygotes, 35 heterozygotes and 15 wild-type homozygotes. We are going to observe the development of these mice and examine the level of D-serine in the organs and the serum. Serine racemase expression is going to be determined by real-time PCR and western blotting. In addition, we are going to establish a serine racemase-knockout strain with the genetic background of the C57BL/6 by continuous backcrossing of serine racemase-deficient mice with C57BL/6 mice. Using these mice we try to elucidate the function of serine racemase and D-serine in the central nerve system. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (4 results)

All 2006 2005

All Journal Article (3 results) Book (1 results)

  • [Journal Article] Mammalisan D-Amino-Acid Oxidase, D-Serine, and Serine Racemase : Recent Progress2006

    • Author(s)
      Ryuichi Konno
    • Journal Title

      Trends in DNA Research (C.R.Woods, ed)(Nova Science Publishers, New York)

      Pages: 103-122

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] D-アミノ酸酸化酵素とその欠損マウスを用いた生体内D-アノ酸の生理的意義2005

    • Author(s)
      金野柳一
    • Journal Title

      ファルマシア 41 (9)

      Pages: 832-856

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] D-Amino-acid oxidase and analysis of physiological function of D-amino acids in the body using the mutant mice lacking D-amino-acid oxidase (in Japanese)2005

    • Author(s)
      Ryuichi Konno
    • Journal Title

      Pharmacia 41

      Pages: 852-856

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Mammalian D-Amino-acid oxidase, D-Serine, and Serine Racemase : Recent Progress. In : Trends in DNA Research (C. R. Woods, ed)_2006

    • Author(s)
      Ryuichi Konno
    • Total Pages
      20
    • Publisher
      Nova Science Publishers
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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