2003 Fiscal Year Annual Research Report

転写因子群による血液細胞・分化の制御機構の解明

Research Project

Project/Area Number	14370040
Research Institution	University of Tsukuba
Principal Investigator	高橋智筑波大学, 基礎医学系, 教授 (50271896)
Keywords	血球分化 / 転写因子 / 初期造血 / Maf転写因子 / GATA転写因子 / 血管内皮 / 中胚葉
Research Abstract	本研究の目的は、血球系転写因子群の血液細胞の分化における機能を明らかにすることであった。現在、血液細胞を含む臓器の分化は、複数の転写因子の幹細胞内でのバランスで決定されるとの考え方が有力であるが、その仮説を個体内で検証した。血球系転写因子群の機能解析を通して、転写因子による血液細胞の分化の方向性の制御機構に、分子レベル・個体レベルで詳細にアプローチを行った。 a)MafB、c-Maf重複欠損マウスの解析: 我々の昨年度までの解析結果より、MafBおよびc-Mafがマクロファージ系列の細胞に発現していることを、個体レベルで確認した。それぞれの単独欠損マウスでは著明な表現型が認められなかったため、MafBおよびc-Mafの重複欠損マウスを作製した。その結果MafB+/-::c-Maf+/-マウスで、マクロファージ系統の細胞の著明な増殖が見られ、リンパ節、脾臓の腫張が観察された。また、それらのマウスでは、抗核抗体値の上昇、皮膚炎等の自己免疫様病態が観察された。以上の事から大Maf群転写因子は、マクロファージ系統の細胞の正常な分化に必須の転写因子であることが示唆された。 b)GATA-1の初期造血の血球分化決定における機能解析: 中胚葉から血球および血管内皮細胞が分化誘導されてくるが、その分子機構はほとんど明らかにされていない。そこで本研究では、初期中胚葉から血球が分化誘導される過程に必須な転写因子の探索を行った。様々な転写因子の発現を細胞レベルで解析したところ、血球の分化と転写因子GATA-1の発現が、ほとんど一致することを明らかにした。このことはGATA-1もしくはGATA転写因子群が、血球分化に必須な転写因子であることを示唆していると考えられた。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Morita M, et al.: "HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin"EMBO J.. 22. 1134-1146 (2003)
[Publications] Yokoyama H, et al.: "Regulation of YB-1 gene expression by GATA transcription factors"Biochem Biophys Res Commun.. 303. 140-145 (2003)
[Publications] Morita M, et al.: "Functional analysis of basic transcription element binding protein by gene targeting technology"Mol Cell Biol.. 23. 2489-2500 (2003)
[Publications] Hirayama A, et al.: "EPR imaging of reducing activity in Nrf2 transcriptional factor-deficient mice"Free Radical Biol.Med.. 34. 1236-1242 (2003)
[Publications] Hirotsune S, et al.: "An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene"Nature. 423. 91-96 (2003)
[Publications] Moriguchi T, et al.: "Distinct response to dioxin in an arylhydrocarbon receptor (AhR)-humanized mouse"Proc Nat Acad Sci. USA. 100. 5652-5657 (2003)
[Publications] Minegishi N, et al.: "Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos"Blood. 102. 896-905 (2003)
[Publications] Wakabayashi J, et al.: "GATA-1 testis activation region is essential for Sertoli cell-specific expression of GATA-1 gene in transgenic mouse"Gene Cells. 7. 619-630 (2003)
[Publications] Hamada M, et al.: "The mouse maf B 5´-upstream fragment directs gene expression in myelomonocytic cells, differentiated macrophages and the ventral spinal cord in transgenic mice"J Biochem.. 134. 203-210 (2003)
[Publications] Yoh K, et al.: "Transgenic overexpression of GATA-3 in Tlymphocytes improves autoimmune glomerulonephritis in mice with a BXSB/MpJ-Yaa genetic background"J Am Soc Nephrol.. 14. 2494-2502 (2003)
[Publications] Wakabayashi N, et al.: "Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation"Nat Genet.. 35. 238-245 (2003)
[Publications] Morito N, et al.: "Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels"Oncogene.. 22. 9275-9281 (2003)
[Publications] Terunuma T, et al.: "Effect of acoustic stress on glucocorticoid receptor mRNA in the cochlea of the guinea pig"Mol Brain Res.. 120. 65-72 (2003)
[Publications] Kajihara M, et al.: "Mouse MafA, homologue of zebrafish Somite Maf1 contributes to the specific transcriptional activity through the insulin promoter"Biochem Biophys Res Commun.. 312. 831-842 (2003)
[Publications] Morito N, et al.: "Nrf2-deficiency improves autoimmune nephritis caused by the fas mutation lpr"Kidney Int.. (in press).
[Publications] Nakatani K, et al.: "Endothelial adhesion molecules in glomerular lesions : Association with their severity and diversity in lupus models"Kidney Int.. (in press).

2003 Fiscal Year Annual Research Report

転写因子群による血液細胞・分化の制御機構の解明

Principal Investigator

高橋 智 筑波大学, 基礎医学系, 教授 (50271896)

Research Products

[Publications] Morita M, et al.: "HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin"EMBO J.. 22. 1134-1146 (2003)

[Publications] Yokoyama H, et al.: "Regulation of YB-1 gene expression by GATA transcription factors"Biochem Biophys Res Commun.. 303. 140-145 (2003)

[Publications] Morita M, et al.: "Functional analysis of basic transcription element binding protein by gene targeting technology"Mol Cell Biol.. 23. 2489-2500 (2003)

[Publications] Hirayama A, et al.: "EPR imaging of reducing activity in Nrf2 transcriptional factor-deficient mice"Free Radical Biol.Med.. 34. 1236-1242 (2003)

[Publications] Hirotsune S, et al.: "An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene"Nature. 423. 91-96 (2003)

[Publications] Moriguchi T, et al.: "Distinct response to dioxin in an arylhydrocarbon receptor (AhR)-humanized mouse"Proc Nat Acad Sci. USA. 100. 5652-5657 (2003)

[Publications] Minegishi N, et al.: "Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos"Blood. 102. 896-905 (2003)

[Publications] Wakabayashi J, et al.: "GATA-1 testis activation region is essential for Sertoli cell-specific expression of GATA-1 gene in transgenic mouse"Gene Cells. 7. 619-630 (2003)

[Publications] Hamada M, et al.: "The mouse maf B 5´-upstream fragment directs gene expression in myelomonocytic cells, differentiated macrophages and the ventral spinal cord in transgenic mice"J Biochem.. 134. 203-210 (2003)

[Publications] Yoh K, et al.: "Transgenic overexpression of GATA-3 in Tlymphocytes improves autoimmune glomerulonephritis in mice with a BXSB/MpJ-Yaa genetic background"J Am Soc Nephrol.. 14. 2494-2502 (2003)

[Publications] Wakabayashi N, et al.: "Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation"Nat Genet.. 35. 238-245 (2003)

[Publications] Morito N, et al.: "Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels"Oncogene.. 22. 9275-9281 (2003)

[Publications] Terunuma T, et al.: "Effect of acoustic stress on glucocorticoid receptor mRNA in the cochlea of the guinea pig"Mol Brain Res.. 120. 65-72 (2003)

[Publications] Kajihara M, et al.: "Mouse MafA, homologue of zebrafish Somite Maf1 contributes to the specific transcriptional activity through the insulin promoter"Biochem Biophys Res Commun.. 312. 831-842 (2003)

[Publications] Morito N, et al.: "Nrf2-deficiency improves autoimmune nephritis caused by the fas mutation lpr"Kidney Int.. (in press).

[Publications] Nakatani K, et al.: "Endothelial adhesion molecules in glomerular lesions : Association with their severity and diversity in lupus models"Kidney Int.. (in press).

高橋智筑波大学, 基礎医学系, 教授 (50271896)