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Regulation of Disease Susceptibility through Gene Introduction of Transcriptiom Factors.

Research Project

Project/Area Number 09557010
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General medical chemistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

YAMAMOTO Masayuki  University of Tsukuba, Institute of Basic Medical Sciences, Professor., 基礎医学系, 教授 (50166823)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Satoru  University of Tsukuba, Institute of Basic Medical Sciences, Lecturer., 基礎医学系, 講師 (50271896)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 1998: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1997: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsc-Maf / transcription factor / transgenic mouse / T lymphocyte / autoimmune disease / differentiation / c-Maf / Tリンパ球 / C-Maf / 細胞分化
Research Abstract

The susceptibility to various diseases is closely related to the balance between T lymphocyte subpopulations (Th1 cells vs. Th2 cells). According to the recent report, Th2 cells were induced by c- Maf which activates the transcription of IL-4 gene. On the basis of these results, we intended to regulate disease susceptibility by utilizing c-Maf for changing the balance between Th1 and Th2 cells.
(1) Generation of transgenic mice which express c-Maf in T lymphocyte lineage. Transgenic mice were generated which express c-Maf under the gene regulatory system of CD2 or LCK in T lymphocytes. Th2 cells were dominant in the mice from the serological analysis. The mice also frequently suffered from lymphoma after 8-10 months old. We are planning to introduce the transgene to the background which shows spontaneous onset of autoimmune diseases and to see whether the transgene will change the disease susceptibility.
(2) Gene disruption of mouse c-maf gene. We completed gene disruption of mouse c-maf gene. c-Maf null mice were mostly lethal at the late stage of embryogenesis and showed defective lens formation. We will search for the influence on T lymphocyte differentiation in the mutant mice.

Report

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

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Yamaguchi,Y.: "Forced GATA-1 expression in the munne mysloid cell line MI : Induction of cMpl expression and megakaryocytic /erythroid differentiation" Blood. 91. 450-457 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harigae,H.: "Deficient heme and globin synthesis in ES cells lacking the erythroid-specific g-aminolevutinate synthess gene" Blood. 91. 798-805 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Minegishi,N.: "A Hernative promoters regulate transcription of the mouse GATA-2 gene" J.Biol.Chem.273. 3625-3634 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai,T.: "Regulation of NF-E2 activity in erytloliulcemia cell differentiation" J.Biol.Chem.273. 5358-5365 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroha,T.: "Ablation of Nrf2 function does not einbellish erythroid or megakaryocytic cell Imeage dysfunction caused by 45 NFE2 gene disrupta" J.Biochem.123. 376-379 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi,Y.: "Machanisms of transcription in eosinophils : GATA-1,but not GATA-2,fronsationt the promoter of the eosinophil gronule major basic protein gene" Blood. 91. 3447-3458 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahashi,S.: "Role of GATA-1 in proliferation and diffrentiation of definitive erythroid and megakoryocytic cells vitro" Blood. 92. 434-442 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harigae,H.: "Diffrencial roles of GATA-1 and GATA-2 in growth and differentiation of mast cells." Genes Cell. 3. 39-50 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Igarashi,K.: "MuHivalent DNA binding complex by small Mof and Buchl as a possible biochemical basis for β-globin locus controle region holoconplex" J.Biol.Chem.273. 11783-11790 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shavit,J.A.: "Impaired megakoryopoicsis and bzhavoral delect in mofG-null mutant mice" Genes Dev.12. 2164-2174 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Cohen-kaminsky,S.: "Chromotin immunoselection defines a TAL-1 target gene" EMBO J.17. 5151-5160 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muto,A.: "Identification of Back2 as a B cell-spcific portner for smoll Mcf proteins that nagatively regulotes immunoglobulin heeay chain 3' inhancer" EMBO J.17. 5734-5743 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwata,T.: "Structure and chromosorne mapping of the human small mafgenes MAFG and MAFK" Cytogenet.Cell Genet. 82. 88-90 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada,T.: "Reduction of DNA binding activity of the GATA-1 transcritihon factor in the optotic process induced by ourexpression of PV.1 in murine erythroleulcenic cells" Expriment.Cell Res.245. 186-194 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahashi,Si.: "Differential regulation of mouse coproporphyrinogen oxidase gene expression in erythroid and non-erythroid cells." Blood. 92. 3436-3444 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suwabe,N.: "GATA-1 regulates growth and differentiation of detinitive erythroid Image cells during in vitro Es'cell differentiation" Blood. 92. 4108-4115 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Motohashi,H.: "A core region of the maf K gene to promoter directs neuron-specific transcription in vivo" Genes Cell. 3. 617-684 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhou,Y.: "Rescue of the embryonic lethcl hemolopitic detects a critical role for GATA-2 in urgenital development" EMBO J. 17. 6689-6700 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuyama,K.: "R411C mutation of the ALAS2 gene encocles a pyndoxine-responsive enzyme with low actrity" British J.Hoematol. 103. 839-841 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Itoh,K.: "Keopl represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the N-terminal Nzh2 domain" Genes Dev.13. 76-86 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi,A.: "Molecular cloning and functional characterization of a new CNC family transcription factor Nrf3" J.Biol.Chem. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Minegishi,N.: "The mouse GATA-2 gene is expressed in the aorta-gurods mesonephros region." Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi, Y.: "Forced GATA-1 expression in the murine myeloid cell line M1 : Induction of c-Mpl expression and megakaryocytic/erythroid differentiation." Blood. 91. 450-457 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harigae, H.: "Deficient heme and globin synthesis in ES cells lacking the erythroid-specific delta-aminolevulinate synthase gene." Blood. 91. 798-805 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Minegishi, N.: "Alternative promoters regulate transcription of the mouse GATA-2 gene." J.Biol.Chem.273. 3625-3634 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai, T.: "Regulation of NF-E2 activity in erythroleukemia cell differentiation." J.Biol.Chem.273. 5358-5365 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuroha, T.: "Ablation of Nrf2 function does not embellish erythroid or megakaryocytic cell lineage dysfunction caused by p45 NF-E2 gene disruption." J.Biolchem.123. 376-379 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi, Y.: "Mechanisms of transcription in eosinophils : GATA-1, but not GATA-2, transactivates the promoter of the eosinophil granule major basic protein gene." Blood. 91. 3447-3458 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahashi, S.: "Role of GATA-1 in proliferation and differentiation of definitive erythroid and megakaryocytic cells in vitro." Blood. 92. 434-442 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harigae, H.: "Differential roles of GATA-1 and GATA-2 in growth and differentiation of mast cells." Genes Cell. 3. 39-50 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Igarashi, K.: "Multivalent DNA binding complex by small Maf and Bach1 as a possible biochemical basis for beta-globin locus control region holocomplex." J.Biol.Chem.273. 11783-11790 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shavit, J.A.: "Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice." Genes Dev. 12. 2164-2174 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Cohen-Kaminsky, S.: "Chromatin immunoselection defines a TAL-1 target gene." ENBO J.17. 5151-5160 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muto, A.: "Identification of Bach2 as a B cell-specific partner for small Maf proteins that negatively regulates immunoglobulin heavy chain 3' enhancer." EMBO. J.17. 5734-5743 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwata, T: "Structure and chromosome mapping of the human small maf genes MAFG and MAFK." Cytogenet.Cell Genet. 82. 88-90 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada, T.: "Reduction of DNA binding activity of the GATA-1 transcription factor in the apoptotic process induced by overexpression of PU.1 in murine erythroleukemia cells" Experiments.Cell Res.245. 186-194 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahashi, S-i.: "Differential regulation of mouse coproporphyrinogen oxidase gene expression in erythroid and non-erythroid cells." Blood. 92. 3436-3444 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suwabe, N.: "GATA-1 regulates growth and differentiation of definitive erythroid lineage cells during in vitro ES cell differentiation." Blood. 92. 4108-4115 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Motohashi, H.: "A core region of the mafK gene I_N promoter directs neuron-specific transcription in vivo." Genes Cells. 3. 617-684 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhou, Y.: "Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA-2 in urogenital development." EMBO J.17. 6689-6700 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furuyama, K.: "R411C mutation of the ALA2 gene encodes a pyridoxine-responsive enzyme with low activity." British J.Haematol.103. 839-841 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Itoh, K.: "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the N-terminal Neh2 domain." Genes Dev.13. 76-86 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi, A.: "Molecular cloning and functional characterization of a new CNC family transcription factor Nrf3." J.Biol.Chem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Minegishi, N.: "The mouse GATA-2 gene is expressed in the aorta-gonads-mesonephros region." Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shavit,J.A.et al: "Impaired megakaryopoiesis and behavioral defects in mafG null mutant mice." Genes Dev.12. 2164-2174 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwata,T.et al: "Structure and chromosome mapping of the human small maf genes MAFG and MAFK." Cytogenet.Cell Genet.82. 88-90 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Motohashi,H.et al: "A core region of the mafK gene In promoter directs neuron-specific transcription in vivo." Genes Cells. 3. 671-684 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagai,T.et al: "Regulation of NF・E2 activity in erythroleukemia cell differentiation." J.Biol.Chem.273. 5358-5365 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda,T.et al: "Ablation of Nrf2 function does not embellish erythroid or megakaryocytic cell lineage dysfunction caused by p45 NF・E2 gene disruption." J.Biochem.123. 376-379 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Igarashi,K.et al: "Multivalent DNA binding complex by small Maf and Bachl as a possible biochemical basis for β-alobin locus control region holocomplex." J.Bio.chem.273. 11783-11790 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Muto,A.et al: "Identification of Bach2 as a B cell-specific partner for small Maf proteins that negatively regulates immunoglobulin heavy chain 3'ehhancer." EMBO J.17. 5734-5743 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Itoh,K.et al: "Keapl represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the N-terminal Neh2 domain." Genes Dev.13. 76-86 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takahashi,S.: "Arrest in erythroid cell development by promoter-specific disruption of GATA-1 gene." J.Biol.Chem.272. 12611-12615 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Onodera,K.: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Proc.Natl.Acad.Sci.USA. 94. 4487-4492 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Furuyama,K.: "Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene." Blood. 90. 822-830 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Itoh,K.: "An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant responsive elements." Biochem.Biophys.Res.Commun.236. 313-322 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minegishi,N.: "Alternative promoters regulate transcription of the mouse GATA-2 gene." J.Biol.Chem.273. 3625-3634 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Harigae,H.: "Deficient heme and globin synthesis in ES cells lacking the erythroid-specific δ-aminolevulinate synthase gene." Blood. (印刷中). 000-000 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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