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Identification of Transcriptional Factor(s) which regulates Ig gene expression

Research Project

Project/Area Number 03670252
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKYUSYU UNIVERSITY

Principal Investigator

NAKASHIMA Manabu  Medical Institute of Bioregulation, Kyusyu University, Assistant, 生体防御医学研究所, 助手 (50198074)

Co-Investigator(Kenkyū-buntansha) KITAMURA Daisuke  Medical Institute of Bioregulation, Kyushu University, Assistant, 生体防御医学研究所, 助手 (70204914)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsImmunoglobulin gene / enhancer / silencer / Transgenic mouse / gene expression / イントロン・エンハンサ- / サイレンサ- / 転写調節
Research Abstract

Immunoglobulin heavy-chain (IgH) gene expression is regulated in a large part by the IgH gene intronic enhancer which is composed of certain protein-binding motifs. These motifs act as a DNA element which is important for the regulation of the IgH gene trasncription. Two of these motifs, HE2 and E6 in the human IgH gene intronic enhancer, are considered to affect the B cell-specific gene expression. E6 was found to function as a silencer in non-lymphoid cells. It is very important to identify the regulatory molecules acting on these elements and their in vivo function. To examine the true function of the HE2 and E6 motifs in vivo, we established transgenic mouse lines. A 3^'deletion mutant of the IgH gene intronic enhancer which includes an active HE2 motif showed almost the same degree of trnascriptional activity and tissue-specificity as the whole IgH gene intronic enhancer. Still more, using the luciferase-assay, it was confirmed at cellular level that the HE2 motif plays an important role in the tissue-specific activity of the IgH gene intronic enhancer. On the other hand, the E6 motif was in some non-B cells.
In transgenic mice, the IgH gene intronic enhancer functioned not only in B-lymphocytes but also in choroid plexus cells which are similar to glial cells. This suggests the existence of common gene expression control mechanisms between the immune system and the nervous system.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Nakashima,M.,Nishimura,Y.,Watanabe,T.: "Recombinant human-nouse chimeric monoclonal antibody specific for human adenocarcinoma associated antigen." Hybridoma. 10. 1-9 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakashima,M.,Watanabe,T.,Koprowski,H.,Schuchter,L.,Steplewski,Z.: "In vitro expansion of malanoma specific,HLA restricted CD8^+ cytotoxic T Tymphocytes." Cellul.Immunol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kitamura,D.,Kudo,A.,Schaal,S.,Muller,W.,Melchers,F.,Rajewsky,K.: "A critical role of λ5 protein in B cell development." Cell. 69. 823-831 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kitamura,D.,Rajewsky,K.: "Targeted disruption of the membrane exon of the μ chain results in loss of heavy chain allelic exclusion." Nature. 356. 154-156 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakashima, M.,Nishimur, Y.,Watanabe, T.: "Recombinant human-mouse chimeric monoclonal antibody specific for human adenocarcinoma associated antigen." Hibridoma. 10. 1-9 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakashima, M.,Watanabe, T.,Koprowski, H.,Schuchter, L.,Steplewski, Z.: "In vitro expansion of melanoma specific, HLA restricted CD8^+ cytotoxic T lymphocytes." Cellul Immunol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kitamura, D.,Kudo, A.,Schaal, S.,Muller, W.,Melchers, F.,Rajewsky, K.: "A critical role of alpha5 protein in B cell development." Cell. 69. 823-831 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kitamura, D.,Rajewsky, K.: "Targeted disruption of the membrane exon of the m chain results in loss of heavy chain allelic exclusion." Nature. 356. 154-156 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakashima,M.,Nishimura,Y.,Watanabe,T.: "Recombinant human-mouse chimeric monoclonal antibody specific for human adenocarcinoma associated antigen." Hybridoma. 10. 1-9 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakashima,M.,Watanabe,T.,Koprowski,H.,Schuchter,L.,Steplewski,Z.: "In vitro expansion of melanoma specific,HLA restricted CD8^+ cytotoxic T lymphocytes." Cellul.Immunol.

    • Related Report
      1992 Annual Research Report
  • [Publications] Kitamura,D.,Kudo,A.,Schaal,S.,Muller,W.,Melchers,F.,Rajewsky,K.: "A critical role of 5 protein in B cell development." Cell. 69. 823-831 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kitamura,D.,Rajewsky,K.: "Targeted disruption of the membrane exon of the chain results in loss of heavy chain allelic exclusion." Nature. 356. 154-156 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Nakashima,Y.Nishimura,T.Watanabe.: "Recombinant humanーmouse chimeric monoclonal antibody specific for human adenocarcinoma associated antigen." Hybridoma. 10. 1-9 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Mori,K.Hirata,M.Kawabuchi,M.Nakashima,T.Watanabe.: "A novel MHC classIーrelated molecule expressed on mouse thymic stroma cells and mature lymphocytes" Immunogenetics. 33. 101-107 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Nakashima,T.Watanabe,H.Koprowski,L.Schuchter,Z.Steplewski.: "In vitro expansion of melanoma specific,HLA restricted CD8+ cytotoxic T lymphocytes." Proc.Ntal.Acad.Sci.U.S.A..

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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