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DEVELOPEMNT OF TRANSGENIC TECHNOLOGY AND IT'S USE FOR CANCER RESEARCH

Research Project

Project/Area Number 09253243
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

YAMAMURA Kenichi  KUMAMOTO UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (90115197)

Co-Investigator(Kenkyū-buntansha) 阿部 訓也  熊本大学, 医学部, 助教授 (40240915)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 1998: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 1997: ¥12,000,000 (Direct Cost: ¥12,000,000)
KeywordsES CELL / GENE TRAP / CRE-LOXP / RECOMBINATIO / KNOCKOUT MOUSE / CHIMERIC MOUSE / ARTIFICIAL CHROMOSOME / 人工細菌染色体 / 酵母人工染色体 / 胚葉体
Research Abstract

Using the recombination system Cre-loxP derived from bacteriophage P1, we developed the gene insertion system. This system comprises of two mutant lox, lox71 and lox66. We constructed a new trap vector that carry this lox71. The method using this trap vector was termed as the exchangeable gene trap, because we can insert any gene of interest after gene trapping. We alaso demonstrated that the efficiency of gene integration was improved by combination of mutant lox71/66 and mutant lox511 that carry mutation in the spacer region. ES cells can be induced to differentiate to form embryoid bodies by removing from feder cells and maintaining in suspension culture. We used this embryoid body formation as a screening system to trap genes involved in cell proliferation and early stages of development. We established 24 trap lines. Among these half of them showed lethilty in development and growth. We isolated the genes trapped by trap vector and tne nucleotide sequences were determined. These s … More eqences were compared with DNA database using balst program. These include several classes of proteins involved in transcription, cell growth, cell division, singal transduction, translation and transportaiton. Among trap lines established, we analyzed two lines in which CBP (creb binding protein) and c-crk genes are disrupted. A heterozygous mouse for CBP mutation is a mouse model for human disease, Rubinstein-Taybi syndrome, and shows most of phenotypes found in human patient. A homozygous mouse is embryonic lethal due to failures of hematopoiesis and vasculogenesis. A homozygous mouse for c-crk mutation did not show any phenotype. However, they died within 24 hours after birth by backcrossing to C57BL/6 suggesting the presence of modifier gene. A method for microinjecting bacterial artificial chromosome has been established and 34 strains of mice that carry bacterial artificial chromosome were generated. Among these, 31 cases are found to have complete bacterial artificial chromosome without any deletion. BACs containing T gene and qkI gene were shown to rescue T mutant and qk mutant, respectively. Less

Report

(3 results)
  • 2000 Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Oike,Y. et al.: "Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice : Implication of a dominant negative mechanism."Human Mol.Genet.. 8. 387-396 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Araki,K. et al.: "Exchangeable gene trap using the Cre/mutated lox system. :"Cell.Mol.Biol.. 45. 737-750 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oike,Y. et al.: "Molecular cloning of the human gene STK10 encoding LOK and comparative chromosomal mapping of the human, mouse and rat"Immunogenetics. 49. 369-375 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Myint,Y.Y. et al.: "Granulocyte/Macrophage colony-stimulating factor and interleukin-3 correct osteopetrosis in mice with osteopetrosis mutant."Amer.J.Pathol.. 154. 553-566 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimada,H. et al.: "Comparison of ES cell fate in sandwiched aggregates and co-cultured aggregates during blastocyst formation by monitored GFP"Mol.Reprod. De. 52. 376-382 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Terauchi,Y. et al.: "Increased insulin sensitivity and hypoglycaemia in mice lackong the p85a subunit of phosphoinositide 3-kinase."Nature Genetics. 21. 230-235 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto,T. et al.: "The mouse interferon-g transgene chronic hepatitis model."Int.J.Mol.Med.:. 3. 517-520 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamura,K.: "Overview of trangenic and gene knockout mice.:"Prog.Exp.Tumor Res.. 35. 13-24 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akbar,S. et al.: "Molecular cloning of the human gene STK10 encoding LOK and comparative chromosomal mapping of the human, mouse and rat"Immunogenetics. 49. 369-375 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanai-Azuma,M. et: "Unique features of dendritic cells in IFN-g transgenic mice : Relevance to cancer development and therapeutic implications."Biochem.Biophis.Res.Comm.. 259. 294-299 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kondo,T. et al.: "Genomic organization and expression analysis of the mouse qkl"Mammal.Genom. 10. 662-669 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamauchi,Y. et: "A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice."Dev.Biol.. 212. 191-203 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamauchi, Y.et al.: "A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice."Dev.Biol.. 212. 191-203 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Araki, K.et al.: "Exchangeable gene trap using the Cre/mutated lox system."Cell.Mol.Biol.. 45. 737-750 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oike, Y.et al.: "runcated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice : Implication of a dominant negative mechanism. of the human, mouse and rat homologues."Human Mol.Genet.. 8. 387-396 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Myint, Y.Y.et al.: "Granulocyte/Macrophage colony-stimulating factor and interleukin-3 correct osteopetrosis in mice with osteopetrosis mutant."Amer.J.Pathol.. 154. 553-566 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Terauchi, Y.et al.: "Increased insulin sensitivity and hypoglycaemia in mice lackIng the p85a subunit of phosphoinositide 3-kinase."Nature Genetics. 21. 230-235 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto, T.et al.: "Chronic hepatitis in interferon-g trangenic mice is associated with elevated CPP32-like activity and interleukin-1b-converting enzyme activity suppression."Jpn.J.Pharmacol.. 79. 289-294 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okamoto, T.et al: "The mouse interferon-g transgene chronic hepatitis model."Int.J.Mol.Med.. 3. 517-520 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamura, K.: "Overview of trangenic and gene knockout mice."Prog.Exp.Tumor Res.. 35. 13-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akbar, S.M.F.et al.: "Unique features of dendritic cells in IFN-g transgenic mice : Relevance to cancer development and therapeutic implications."Biochem.Biophis.Res.Comm.. 259. 294-299 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oike et al.: "Mice homozygous for a truncated form of a CREB-binding protein (CBP) exhibit defects in hematopoiesis and vasculo-angiogenesis."Blood. 93. 2771-2779 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimada, H.et al.: "Comparison of ES cell fate in sandwiched aggregates and co-cultured agregates during blastocyst formation by monitored GFP expression."Mol.Reprod.Dev.. 52. 376-382 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kondo, T.et al.: "Genomic organization and expression analysis of the mouse qkI locus."Mammal.Genome. 10. 662-669 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuda,J.et al.: "Transgenic mouse expressing full-length hepatitis C virus cDNA." Jpn.J.Cancer Res.89. 150-158 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sugimoto,T.et al.: "Region-specific expression of murine Hox genes implies the Hox coed-mediated patterning of the digestive tract." Genes to Cells. 3. 51-64 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujimoto,S.et al.: " Analysis of the murine Hoxa-9 cDNA:an a.ternatively spliced transcript encodes a truncated protein lacking the homeodomain." Gene. 209. 77-85 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawakami,S.,er al.: "Tctex3, related to Drosophila Polycomblike,is expressed in male germ cells and mapped to the mouse t-complex." Mammalian Genome. 9. 874-880 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oike,Y.et al.: "Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in male:Implication of a dominant negative mechanism." Human Mol.Genet.8. 387-396 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Araki, K.et al.: "Targeted integration of DNA using mutant lox sites in embryonic stem cells." Nucleic Acid Res.25. 868-872 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kimura, S.et al.: "2.1 kb 5'-flanking region of the brain type dystrophin gene directs the expression of lacZ in the cerebral cortex, but not in the hippocampus." J.Neurol.Sci.147. 13-20 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Araki, K.et al.: "Efficinecy of recombination by Cre transient expression in embryonic stem cells:comparison of various promoters." J.Biochem.122. 977-982 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sekimoto, T.et al.: "Region specific expression of murine Hox genes implies the Hox code-mediated patterning of the digestive tract." Genes to Cells.(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2019-02-15  

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