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Analysis of mast cell-specific transcription by mutant mice

Research Project

Project/Area Number 11694272
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionOsaka University

Principal Investigator

MORII Eiichi (2000)  Osaka Univ Graduate Sch of Med, Assist Prof, 医学系研究科, 助手 (10283772)

北村 幸彦 (1999)  大阪大学, 医学系研究科, 教授 (70028520)

Co-Investigator(Kenkyū-buntansha) ADACHI Shiro  Osaka Univ Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40301254)
ITO Akihiko  Osaka Univ Graduate School of Medicine Assist, Profess, 医学系研究科, 助手 (80273647)
JIPPO Tomoko  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70252658)
森井 英一  大阪大学, 医学系研究科, 助手 (10283772)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsmast cell / transcription / MITF / mutant mice / cell specific / mi転写因子 / 突然変異マウス / 転写因子ネットワーク / 発現調節機構 / Mi転写因子 / PEBP2 / CBF
Research Abstract

MITF is a basic-helix-loop-helix leucine zipper (bHLH-Zip) transcription factor, which is important for the development of mast cells. The mi locus encoding MITF possesses various mutant alleles. These are useful for examining the structure-function relationship of MITF in vivo. Mast cells of mi/mi genotype express normal amount of abnormal MITF (mi-MITF), whereas mast cells of tg/tg genotype do not express any MITFs. Mast cells of mi/mi mice show more severe abnormalities than those of tg/tg mice, indicating that the mi-MITF possesses the inhibitory function. The MITF encoded by the mi^<ce> mutant allele (ce-MITF) lacks the Zip domain. We examined the importance of the Zip domain using mi^<ce>/mi^<ce> mice. The amounts of c-kit, granzyme B (Gr B), and tryptophan hydroxylase (TPH) mRNAs decreased in mast cells of mi^<ce>/mi^<ce> mice to levels comparable to those of tg/tg mice, and the amounts were intermediate between those of +/+ mice and those of mi/mi mice. Gr B mediates the cytotoxic activity of mast cells, and TPH is a rate-limiting enzyme for the synthesis of serotonin. The cytotoxic activity and serotonin content of mi^<ce>/mi^<ce> mast cells were comparable to those of tg/tg mast cells, and were significantly higher than those of mi/mi mast cells. The phenotype of mi^<ce>/mi^<ce> mast cells was similar to that of tg/tg mast cells rather than to that of mi/mi mast cells, suggesting that the ce-MITF had no functions. The Zip domain of MITF appeared to be important for the development of mast cells. We also revealed that MITF played an important role in the transcription of mouse mast cell protease (mMCP)-6, -7, alpha-melanocyte stimulating hormone receptor, N-deacetylase N-sulfotransferase 2 genes. MITF regulated their transcription through the interaction of other transcription factors, such as PEBP2/CBF, c-Jun and GABP.MITF appeared to play a crucial role in the transcriptional regulation of mast cell specific genes.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Ito A.: "Inhibitory effect of the transcription factor encoded by the mi mutont allele in enltured mart cells of mice"Blood. 93. 1189-1196 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogihara H: "Inhibitory effect of tranociption factor encoded by mutant mi alled to tranactiantion of MMCP gene"Boold. 97. 645-651 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito A.: "Inhibitory effect of metural killer activity of MZTF enrodel by the muten mi alleds of nice"Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morii E.: "Impoitanc of lenicne Zpere domes of MITF for differention of mast cells demmatrteted using mi^<・ce>/mi^<・ce> matat mice"Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morri E.: "Inhibitory effect of MITF encoded by the mutat mi elledle an GABP medicted transupt expression in muse mast cells."Boold. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jippo T: "Tissue-dependent altenation of protesae expression phentype in munine peritoneal mast cells that were gentcailly labeled coitl GFP"Am J.Rattol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitammura Y.: "Mast Cells and Basophilo"G.Morone, LM.Lichtenstrion , SJ Galls eds.Acadenic Press. 707 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito A: "Inhibitory effect of the transcription factor encoded by the mi mutant allele in cultured mast cells of mice."Blood. 93. 1189-1196 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jippo T: "Deficient transcription of mouse mast cell protease 4 gene in mutant mice of mi/mi genotype."Blood. 93. 1942-1950 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato M: "Microphthomia-associated transcription factor interacts with PU.1 and c-Fos : determination of their subcellelar localization."Biochem Biophys Res Comm. 254. 384-387 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kim DK: "Different effect of various mutant MITF encoded by mi, Mi^<or>, or Mi^<wh> allele on phenotype of murine mast cells."Blood. 93. 4179-4186 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogihara H: "Synergy of PEB2/CBF with mi transcription factor (MITF) for transcription of mouse mast cell protease 6 gene."Oncogene. 18. 4632-4639 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morii E: "Identification of the region of mi transcription factor (MITF) which is responsible for the synergy with PEBP2/CBF."Biochem Biophys Res Comm. 261. 53-57 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Adachi S: "Involvement of mi-transcription factor (MITF) in expression of a melanocyte stimulating hormone receptor in cultured mast cells of mice."J Immunol. 164. 855-860 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ge Y: "Independent influence of strain difference and mi transcription factor (MITF) on the expression of mouse mast cell chymases."Am J Pathtol. 158. 281-292 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogihara H: "Inhibitory effect of transcription factor encoded by mutant mi microphthalmia allele on transactivation of mouse mast cell protease 7 gene."Blood. 97. 645-651 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morii E: "Importance of leucine zipper domain of mi transcription factor (MITF) for differentiation of mast cells demonstrated using mi^<ce>/mi^<ce> mutant mice of which MITF lacks the zipper domain."Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito A: "Inhibitory effect on natural killer activity of microphthalmia transcription factor encoded by the mutant mi allele of mice."Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morii E: "Inhibitory effect of MITF encoded by the mutant mi allele on GABP-mediated transcript expression in mouse mast cells."Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jippo T: "Tissue-dependent alteration of protease expression phenotype in murine peritoneal mast cells that were genetically labeled with green fluorescent protein."Am J Pathol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morii E.: "Importance of leucine zipper domain of MITF for differentiation of mast cells demonstrated using mi^<ce>/mi^<ce> mice"Blood. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Morii E.: "Inhibitory offect of MITF encoded by the mutant mi allele on GABP-mediated transcript expression"Blood. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogihara H.: "Inhibitory effect of Transorptr doctor encoded by mutant mi allel on transcription of MMCP-7 gene"Blood. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitamara Y.: "Mutant mice a useful tool for studying development of mast cells."Int.Arch.Allergy Immunal. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Ge Y.: "Independent influence of strain difference and mi-transcription factor on the expression of mast cell chymases"Am J Pathol. 158. 281-292 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitamura Y.: "mi transcription factor as a regulution of mast cell differentiation"Int J.Hematol. 71. 197-202 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitamura Y.: "Mast Cells and Bosophilo in ploysiology. Pathology and Host *"Academic Press. 707 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ito A: "Inhibitory effect of the transcription factor encoded by the mi mutant allele in cultured mast cells of mice"Blood. 93. 1189-1196 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jippo T.: "Deficient Transcription of mouse mast cell protease 4 gene in mutant mice of mi/mi genotype"Blood. 93. 1942-1950 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kim DK: "Different effect of various mutant MITF-encoded by mi,Mi^<or>, or Mi^<wh> allele on phenotype of murine mast cells"Blood. 93. 4179-4186 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogihara H: "Synergy of PEBP2/CBF with mi transcription factor for transcription of mouse mast cell protease 6 gene"Oncogene. 18. 4632-4639 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Adachi S.: "Involvement of MITF in expression of α melanocyte stimulating hormone receptor in cultured mast cells"J. Immunol. 164. 855-860 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito A: "A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation"EMBO J.. 19. 562-571 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitamura Y.: "Encyclopedia of Life Sciences"Mcmillan Reference (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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