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Construction of mouse embryonic stem cells for the detection of gene mutation

Research Project

Project/Area Number 08559016
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 広領域
Research InstitutionNational Institute of Health Sciences

Principal Investigator

INOUE Tohru  National Institute of Health Sciences, Division of cellular and molecular toxicology, director, 安全性生物試験研究センター・毒性部, 部長 (50100110)

Co-Investigator(Kenkyū-buntansha) SAGA Yumiko  National Instituteof Health Seiences, Divesion of cellular and molecular toxicology, section chief, 安全性生物試験研究センター・毒性部, 室長 (50221271)
HIRABAYASHI Yoko  National Instituteof Health Seiences, Divesion of cellular and molecular toxicology, senior researrcher, 安全性生物試験研究センター・毒性部, 主任研究官 (30291115)
TAKAGI Atsuya  National Instituteof Health Seiences, Divesion of cellular and molecular toxicology, senior researrcher, 安全性生物試験研究センター・毒性部, 主任研究官 (00179417)
藤本 成明  広島大学, 原爆放射能医学研究所・予防腫瘍, 助教授 (40243612)
梅村 隆志  国立医薬品食品衛生研究所, 安全性生物試験研究センター・毒性部, 主任研究官 (50185071)
能美 健彦  国立衛生試験所, 変異遺伝部, 室長 (30150890)
佐井 君江  国立衛生試験所, 毒性部, 研究員 (20195960)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsEmbryonic stem cell / developmental toxicity / gene mutation / 分化 / 突然変異検出系
Research Abstract

The mouse ES cells can be maintained in tissue culture with pluripotency. ES cells can also be induced to differentiate in vitro. These properties make it an excellent tool for the study of early embryogenesis and, potentially, teratogenesis in vitro. We have established genetic reporter systems in the ES cells for the detection of mutations. E.coli xanthine-guanine phosporibosyl transferase (XPRT) gene (gpt) was transfected to the HPRT- ES cells. After transfection with the gpt gene (pSV2-gpt), surviving cells producing XPRT can be selectively grown with xanthine as the sole precursor for guanine nucleotide formation in a medium containing inhibitors (aminopterin and mycophenolic acid) that block de novo purinenucleotide synthesis. After methyl methane sulfonate (MMS) exposure, signifcant increases of 6-TG resistant colony were observed.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Saga Y, Inoue T et al: "Mesp1 is expressed in the heart precursor cells and required for the formation of a single heart tube"Development. 126. 3437-3447 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sasaki H, Hirabayashi Y., Inoue T. et al.: "A fraction unresponsive to growth inhibition by TGF-beta among the high-proliferative potential progenitor cells in bone marrow of p53-deficient mice"Leukemia. 1. 239-244 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 平林容子、井上達: "胚幹細胞や遺伝子導入マウスによる胎生期造血研究"造血因子. 3. 32-39 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 井上達: "内分泌撹乱とホルモン様化学物質"Environ. Mutagen. Res.. 21. 255-266 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 高木篤也: "内分泌撹乱物質の毒性試験法、新たな試験法の開発1.胚幹細胞を用いた検討"シュプレンガーフェアラーク東京. (出版予定) (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inoue T: "Eds. Griffiths SA and Lumley CE, Kluewer Academic Publishers, London"Biotechnologycall-derived pharmaceuticals in Japan : Present and future prospects, In Safety Evaluation of Biotechnologycally-derived phrmaceuticals : Fachilitating a scientific approach, Proceedings of a CMR International Workshop held at Ashdown Park Hotel, Wych Cross, UK. 51-63 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saga Y, Miyagawa-Tomita S, Takagi A, Kitajima S, Miyazaki Ji, Inoue T: "MesP1 is expressed in the heart precursor cells and required for the formation of a single heart tube"Development. 126(15). 3437-3447 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sasaki H Matsuda M Lu Y Ikuta K, Matuyama S, Hirabayashi Y, Mitsui H, Matsumura T Muramatsu M Tsukada T, Aizawa S, and Inoue T.: "A fraction unresponsive to growth inhibition by TGF-β among the high-proliferative potential progenitor cells in bone marrow of p53-deficient mice"Leukemia. 11. 239-244 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoko Hirabayashi, Tohru Inoue: "Embryonal hemopoiet,ic study using embryonic stem cells and transgenic mice"Hematopoietic Factor. 3. 32-39 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Momma, J., Kitajima S., Inoue T.: "The guinea-pig skin sensitization test revisited: an evaluation formula to predict possible sensitization levels for eight chemicals used in housefould products." Toxicology. 126. 75-82 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirabayashi Y., Inoue T.et al.: "Cell kinetics of hemapoietic colony-foming units in spleen(CFU-S)in young and old mice." Mechanisms of Ageing and Development.101. 221-231 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inoue T: "Hematopoietic cell growth factors and their receptors" International Journal of Hematology. 67. 101-103 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 菅野純、相賀裕美子、井上達: "化学物質の生物毒性試験-内分泌障害性を中心に" 組織培養工学. 24. 268-271 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inoue T.: "(eds.DnArcy PF & Harron DWG.) Queens University of Belfast" Concept of a relavant animal model,In: Proceedings of the Forth International Conference on Harmonisation, 209-223 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inoue T: "Eds.Griffiths SA and Lumley CE,Kluewer Academic Publishers,London" Biotechnologycall-derived pharmaceuticals in Japan: Present and future prospects,In Safety Evaluation of Biotechnologycally-derived phrmaceuticals: Facilitating a scientific approach,Proceedings of a CMR International Workshop held at Ashdown Park Hotel,Wych Cross,UK, 51-63 (1988)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirabayashi Y: "Call kinetics of hemopoietic colony-forming units in spleen(CFU-S)in young and old mice." Mechanisms of Ageing and Development. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirabayashi Y: "The p53-deficient hemopoietic stem cells:their resistance to radiation-apoptosis,but lasted transiently" Leukemia. 11(S3). 489-492 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida K: "Calorie restriction reduces the incidence of myeloid leukemia induced by a single whole-body radiation in C3H/He mice" Pro Natl Acad Sci,USA. 94. 2515-2519 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishijima I: "Hematopoietic and lymphopoietic responses in human granulocyte-macrophage colony-stimulating factor (GM-CSF)receptor transgenic mice injected with human GM-CSF" Blood. 90. 1031-1038 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sasaki H: "A fraction unresponsive to growth inhibition by TGF-beta among The high-proliferative potential progenitor cells in bone marrow of p53-deficient mine" Leukemia. 11. 239-244 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inoue T: "Model of MDS-like myelodysplasia that transforms into single lineage-hemopoietic malignancies upon transplantation--" Intnt'l J Ped Hematl/Oncol. 4. 221-230 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inoue T,Hirabayashi Y.他: "Hair follicle dermal papilla cell lines from p53-knockout mice." J.Dermatological Science. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Inoue T,Hirabayash Y.他: "Model of MDS-like myelodysplasia that transforms into single lineage-hematopoietic malignancies upon transplantation implication for pediatric." Int J Ped Hematl/Oncol. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirabayash Y,Inoue T他: "The p53-deficient hemopoietic stem cells : Their resistance to radiation-papooses,but lasted transiently." Leukemia. (in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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