2000 Fiscal Year Annual Research Report

外来異物に対する信号伝達機構を利用した環境モニター動物の開発

Research Project

Project/Area Number	12557015
Research Institution	University of Tsukuba
Principal Investigator	山本雅之筑波大学, 基礎医学系, 教授 (50166823)
Co-Investigator(Kenkyū-buntansha)	小林麻己人筑波大学, 基礎医学系, 講師 (50254941)
Keywords	異物代謝 / 環境異物 / 転写制御 / モデル動物 / bZip型転写因子 / bHLH-PAS型転写因子
Research Abstract	今年度は以下の成果を得た. 1)毒性化学物質に対するNeh2-betaGalマウスの反応性の検定様々な毒性化学物質は,体内で異物代謝第1相の酵素群による代謝をうけ,親電子性物質に変換され,さらに,異物代謝第2相の酵素群の誘導に重要であるNrf2蛋白質を安定化させる.Neh2ドメインはこの安定化に重要な領域である.Neh2-betaGal融合蛋白質を発現するマウスに,BHAを投与したところ,肝臓と小腸において,Neh2-betaGalが安定化して蓄積することが観察された.これにより,このマウスを毒性化学物質のモニターマウスとして利用できる可能性が示唆された. 2)ゼブラフィッシュCYP4501A1・GST-Piレポーター遺伝子導入フィッシュの作製ゼブラフィッシュのCYP4501A1及びGST-Piの遺伝子を単離した.薬物処理胚を用いて発現解析を行ったところ、それぞれ第1相及び第2相誘導剤で発現誘導されることがわかった。この結果は、魚類における異物代謝酵素遺伝子も、哺乳類と同様のしくみで薬物により誘導されることを示唆しており、異物代謝システムが脊椎動物種間で保存されていると理解された。現在、環境モニターフィッシュの作出を目的に、上記遺伝子のプロモーター領域にGFP遺伝子を接続した構築をもつトランスジェニックフィッシュの作製を行っている。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Nishimura,S.: "A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene."Mol.Cell.Biol.. 20. 713-723 (2000)
[Publications] Pan,X..: "Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions."J.Biochem.. 127. 105-112 (2000)
[Publications] Kobayashi,A.: "A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through BTB/ POZ domain."Mol.Cell.Biol.. 20. 1733-1746 (2000)
[Publications] Onodera,K.: "Perinatal synthetic lethality and hematopoietic defects in compound mafG : : mafK mutant mice."EMBO J. 19. 1335-1345 (2000)
[Publications] Katsuoka,F.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells."EMBO J.. 19. 2980-2991 (2000)
[Publications] Ishii,T.: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole."Carcinogenesis. 21. 1013-1016 (2000)
[Publications] Hoshino,H.: "Oxidative stress abolishes leptomycine B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element."J.Biol.Chem.. 275. 15370-15376 (2000)
[Publications] Ishii,T.: "Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages."J.Biol.Chem.. 275. 16023-16029 (2000)
[Publications] Takahashi,S.: "GATA factor transgenes under GATA-1 locus control rescue germ line GATA-1 mutant deficiencies."Blood. 96. 910-916 (2000)
[Publications] Takahashi,S-I.: "Cloning of a coproporphyrinogen oxidase promoter regulatory element binding protein."Biochem.Biophys.Res.Commun.. 2732. 596-602 (2000)
[Publications] Hayes,J.D.: "The Nrf2 transcription factor contributes both to the basal expression of glutathion S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin."Biochem.Soc.Trans.. 28. 33-41 (2000)
[Publications] Zhou,Y.: "GATA2 is required for the generation of V2 intemeurons."Development. 127. 3829-3838 (2000)
[Publications] Toki,T.: "Functional characterization of the two alternative promoters of human p45 NF-E2 gene."Exp.Hematol.. 28. 1113-1119 (2000)
[Publications] Wakabayashi,N.: "A novel cis-acting element regulates HES-1 gene expression in P19 embryonal carcinoma cells treated with retinoic acid."J.Biochem.. 128. 1087-1095 (2000)
[Publications] Motohashi,H.,: "Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins."Cell. 103. 865-875 (2000)

2000 Fiscal Year Annual Research Report

外来異物に対する信号伝達機構を利用した環境モニター動物の開発

Principal Investigator

山本 雅之 筑波大学, 基礎医学系, 教授 (50166823)

Research Products

[Publications] Nishimura,S.: "A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene."Mol.Cell.Biol.. 20. 713-723 (2000)

[Publications] Pan,X..: "Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions."J.Biochem.. 127. 105-112 (2000)

[Publications] Kobayashi,A.: "A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through BTB/ POZ domain."Mol.Cell.Biol.. 20. 1733-1746 (2000)

[Publications] Onodera,K.: "Perinatal synthetic lethality and hematopoietic defects in compound mafG : : mafK mutant mice."EMBO J. 19. 1335-1345 (2000)

[Publications] Katsuoka,F.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells."EMBO J.. 19. 2980-2991 (2000)

[Publications] Ishii,T.: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole."Carcinogenesis. 21. 1013-1016 (2000)

[Publications] Hoshino,H.: "Oxidative stress abolishes leptomycine B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element."J.Biol.Chem.. 275. 15370-15376 (2000)

[Publications] Ishii,T.: "Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages."J.Biol.Chem.. 275. 16023-16029 (2000)

[Publications] Takahashi,S.: "GATA factor transgenes under GATA-1 locus control rescue germ line GATA-1 mutant deficiencies."Blood. 96. 910-916 (2000)

[Publications] Takahashi,S-I.: "Cloning of a coproporphyrinogen oxidase promoter regulatory element binding protein."Biochem.Biophys.Res.Commun.. 2732. 596-602 (2000)

[Publications] Hayes,J.D.: "The Nrf2 transcription factor contributes both to the basal expression of glutathion S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin."Biochem.Soc.Trans.. 28. 33-41 (2000)

[Publications] Zhou,Y.: "GATA2 is required for the generation of V2 intemeurons."Development. 127. 3829-3838 (2000)

[Publications] Toki,T.: "Functional characterization of the two alternative promoters of human p45 NF-E2 gene."Exp.Hematol.. 28. 1113-1119 (2000)

[Publications] Wakabayashi,N.: "A novel cis-acting element regulates HES-1 gene expression in P19 embryonal carcinoma cells treated with retinoic acid."J.Biochem.. 128. 1087-1095 (2000)

[Publications] Motohashi,H.,: "Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins."Cell. 103. 865-875 (2000)

山本雅之筑波大学, 基礎医学系, 教授 (50166823)