• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

Development of rat models for human epilepsy by methods of gene modification

Research Project

Project/Area Number 16200029
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionKyoto University

Principal Investigator

SERIKWA Tadao  Kyoto University, Graduate School Medicine, Professor (30025655)

Co-Investigator(Kenkyū-buntansha) KURAMOTO Takashi  Kyoto University, Graduate School of Medicine, Associate Professor (20311409)
MASHIMO Tomoji  Kyoto University, Graduate School of Medicine, Research Associate Professor (80397554)
SHINOHARA Takashi  Kyoto University, Graduate School of Medicine, Professor (30322770)
Project Period (FY) 2004 – 2007
KeywordsRat / Epilepsy / Mutagenesis / Etyl nitrosourea / Disease model / Chlorambucil / Epilepsy gene / Gene-modified rat
Research Abstract

The aim of this study was the generation and partial characterization of mutant rats that show alteration in epilepsy related genes by screening of ENU- or chlorambucil-induced mutants. Although chlorambucil turned out to be not very efficient in our approach, a recessive mutation with a dwarf phenotype was obtained and is maintained by full-sib mating. We have furthermore developed a new, efficient approach that combines two methods : a high-throughput, low-cost screening assay that uses the phage Mu transposition reaction, and intracytoplasmic sperm injection (ICSI) for the recovery of the rare heterozygous genotypes from our newly generated frozen sperm repository, the Kyoto University Rat Mutant Archive (KURMA). This Mu transposition reaction can be combined with DNA pooling and therefore facilitates an efficient screening approach for mutagenized animals, termed MuT-POWER (Mu Transpositon Poling method With sequencer). The number of G1 DNA and sperm samples has already expanded to 5,000, and we could find 18 point mutations in epilepsy-related genes. Rats with a missense mutation in sodium channel SONIA gene were recovered from cryopreserved sperm by ICSI and a strain with the mutation has been generated. The rats showed a high sensitivity for pentylenetetrazol-induced convulsions and hot-water-induced convulsion, suggesting that they would be possible models for human heat-sensitive convulsions or GEFS+ patients. KURMA virtually allows the production of any rat model resembling human diseases.

  • Research Products

    (26 results)

All 2008 2007 2006 Other

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (16 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Progress and prospects in rat genetics: a community view.2008

    • Author(s)
      Aitman TJ, et. al.
    • Journal Title

      Nat Genet. 40(5)

      Pages: 516-522

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] AnENU-induced mutant archive for gene targeting in rats.2008

    • Author(s)
      Mashimo T, et. al.
    • Journal Title

      Nat Genet. 40(5)

      Pages: 514-515

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Progress and prospects in rat genetics : a community view2008

    • Author(s)
      Aitman, TJ., et. al.
    • Journal Title

      Nat Genet 40(5)

      Pages: 516-522

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An ENU-induced mutant archive for gene targeting in rats2008

    • Author(s)
      Mashimo, T., et. al.
    • Journal Title

      Nat Genet 40(5)

      Pages: 514-515

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Generation of rat offspring derived from cryopreserved spermatozoa in Japanese National Bioresources2007

    • Author(s)
      Kashiwazaki N, et. al.
    • Journal Title

      Reprod Fertil Dev., 19(1)

      Pages: 124-125

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Generation of rat offspring derived from cryopreserved spermatozoa in Japanese National Bioresources2007

    • Author(s)
      Kashiwazaki, N., et. al.
    • Journal Title

      Reprod Fertil Dev 19(1)

      Pages: 124-125

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rats produced by interspecies spermatogonial transplantation in mice and in vitro microinsemination2006

    • Author(s)
      Shinohara T, et. al.
    • Journal Title

      Proc Natl Acad Sci USA 103(37)

      Pages: 13624-13628

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Rats produced by interspecies spermatogonial transplantation in mice and in vitro microinsemination2006

    • Author(s)
      Shinohara, T., et. al.
    • Journal Title

      Proc Natl Acad Sci USA 103(37)

      Pages: 13624-13628

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Gene-targeted rat models of human epilepsy efficiently developed by ENU mutagenesis.2007

    • Author(s)
      Mashimo T, et. al.
    • Organizer
      The 2007 meeting on Rat Genomics & Models
    • Place of Presentation
      Cold Spring Harbor
    • Year and Date
      20071206-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Gene-targeted rat models of human epilepsy efficiently developed by ENU mutagenesis2007

    • Author(s)
      Mashimo, T., et. al.
    • Organizer
      The 2007 meeting on Rat Genomics & Models
    • Place of Presentation
      Cold Spring Harbor, New York, USA
    • Year and Date
      20071206-09
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ENUミュータジェネシスにより作製されたScnla遺伝子変異ラット2007

    • Author(s)
      真下知士, ら
    • Organizer
      Neuro2007
    • Place of Presentation
      横浜
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ENUミュータジェネシスによるSCN1A遺伝子変異ラットの開発2007

    • Author(s)
      真下知士, ら
    • Organizer
      第54回 日本実験動物学会総会
    • Place of Presentation
      東京
    • Year and Date
      20070523-25
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Generation of rat offspring derived from cryopreserved spermatozoa in Japanese National Biorecources2007

    • Author(s)
      Kashiwazaki N, et. al.
    • Organizer
      The 33rd Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Kyoto
    • Year and Date
      20070106-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ナトリウムチャンネルScnla変異ラットの特性解析2007

    • Author(s)
      鶴見東志子, ら
    • Organizer
      第96回 関西実験動物研究会
    • Place of Presentation
      京都
    • Year and Date
      2007-12-14
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ENUミュータジェネシスにより作製したSCN1A遺伝子変異ラットの特徴について2007

    • Author(s)
      真下知士, ら
    • Organizer
      第3回 日本てんかん学会近畿地方会
    • Place of Presentation
      京都
    • Year and Date
      2007-11-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] MuT-POWER: a high-throughput DNA screening method for detecting ENU-induced mutations2006

    • Author(s)
      Mashimo T, et. al.
    • Organizer
      20th International Mouse Genome Conference,
    • Place of Presentation
      South Carolina
    • Year and Date
      20061112-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] MuT-POWER : a high-throughput DNA screening method for detecting ENU-induced mutations2006

    • Author(s)
      Mashimo, T., et. al.
    • Organizer
      20th International Mouse Genome Conference
    • Place of Presentation
      South Carolina
    • Year and Date
      20061112-16
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] MuT-POWER: ENUミュータジェネシスにおける新規DNAスクリーニング法2006

    • Author(s)
      真下知士, ら
    • Organizer
      第53回 日本実験動物学会総会
    • Place of Presentation
      神戸
    • Year and Date
      20060511-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] てんかんに関連する16遺伝子についてのラットSNP解析2006

    • Author(s)
      徳田智子, ら
    • Organizer
      第53回 日本実験動物学会総会
    • Place of Presentation
      神戸
    • Year and Date
      20060511-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 『ラット胚・精子の超低温保存と個体復元技術マニュアル(DVD版)』の作製2006

    • Author(s)
      滝澤明子, ら
    • Organizer
      第92回 関西実験動物研究会
    • Place of Presentation
      京都
    • Year and Date
      2006-12-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ENUミュータジェネシスによるラットリソース:新規てんかんモデルの開発2006

    • Author(s)
      真下知士, ら
    • Organizer
      第92回 関西実験動物研究会
    • Place of Presentation
      京都
    • Year and Date
      2006-12-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ENUミュータジェネシスによる新規ラットリソース資源2006

    • Author(s)
      真下知士, ら
    • Organizer
      第23回 日本疾患モデル学会
    • Place of Presentation
      渋川
    • Year and Date
      2006-12-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] MuT-POWER: A novel efficient screening method in gene-drivenENU mutagenesis2006

    • Author(s)
      Tokuda S, et. al.
    • Organizer
      Workshop on Immunology, Cancer, and Aging
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-02-04
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] MuT-POWER : A novel efficient screening method in gene-driven ENU mutagenesis2006

    • Author(s)
      Tokuda, S., et. al.
    • Organizer
      Workshop on Immunology, Cancer and Aging
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-02-04
    • Description
      「研究成果報告書概要(欧文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.anim.med.kyoto-u.ac.jp/research.htm

  • [Patent(Industrial Property Rights)] 標的遺伝子中にミスマッチを有する生物のスクリーニング方法2006

    • Inventor(s)
      真下知士、柳原克彦、徳田智子、芹川忠夫
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Number
      特願 2006-3855
    • Filing Date
      2006-01-11
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi