1999 Fiscal Year Annual Research Report

顆粒球造血の細胞内情報伝達機構の解明

Research Project

Project/Area Number	11307015
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	Kyushu University
Principal Investigator	仁保喜之九州大学, 大学院・医学系研究科, 教授 (60091287)
Co-Investigator(Kenkyū-buntansha)	浅野嘉延九州大学, 医学部, 助手 (60271110) 権藤久司九州大学, 医学部, 助手 (10253428) 岡村孝九州大学, 医学部, 講師 (30136436) 下田和哉九州大学, 医学部, 助手 (90311844)
Keywords	好中球 / 細胞内情報伝達 / 分化 / Jakキナーゼ / Tyk2 / Stat
Research Abstract	G-CSFの増殖シグナルはJakキナーゼにより伝達される。G-CSFのレセプターへの結合後、Jak1,Jak2,Tyk2が活性化される。報告されたJak1,Jak2欠損マウスの表現型によるとJak1,Jak2の欠損は顆粒球の増殖に影響を与えていない。この事よりG-CSFによる好中球の増殖には、G-CSFにより活性化される残りのJakキナーゼであるTyk2が必須であるか、または1種類のJakキナーゼの欠損を他のJakキナーゼが補完している可能性が想定され、この点を生体内で明確にするため、Tyk2欠損マウスを作成をおこなった。開始コドンを含むTyk2DNAの第1Exsonをneomycin registance geneで置換し、targeting constractを作製しES細胞に遺伝子導入した。相同組み換えが生じたES細胞をmouse blast cystに導入し、chimera miceを得た後、交配後、2個の独立したクローン由来のTyk2欠損マウスが得られた。Tyk2の欠損は生体の発育、生存に必須ではなく、現在その表現系を解析中である。また、G-CSFの文化シグナルは、そのレセプターのC末50塩基を介して伝達される。これに関与するシグナル伝達物質のクローニングを行っている。IL-3依存性細胞株に野生型G-CSFレセプターとC末をわずかに欠失したレセプターを導入した細胞をG-CSFで刺激後、両者より得られたcDNAをsubtractionし、複数個の遺伝子をクローニングした。現在これらの遺伝子の発現をNorthern blottingで検討中である。

Research Products
(24 results)

All Other

All Publications (24 results)

[Publications] Niho Y,: "Mokecular Biology Hematological Disorders"Intermal Medicine. 38. 77-78 (1999)
[Publications] Iwasaki H,: "Production of soluble granulocyte colony-stimulating factor receptors from myelomonocytic cells."Mizuno S.. 163. 6907-6911 (1999)
[Publications] Mizuno S.: "Interferon-γ pervents apoptosis Epstein-Barr virus-infected natural kikker cell leukemia in an autocrine fashion,"Blood. 93. 3494-3504 (1999)
[Publications] Stem Cells: "Effect of interleukin 10 on the hematopoietic progenitor cells patients with aplastic anemia."Stem Cells. 17. 147-151 (1999)
[Publications] Uchida N,: "Differential gene expression of human telomerase-associated protein hTERT and TEP in human hematopietic cells."Leuk Res. 23. 1127-1132 (1999)
[Publications] Okuma K.: "Idenfication of a nobel bovine protein which in involved in human T-cell leukemia virus type I(HTLV-1)-induced syncytium for formation."Arch Virol. 144. 1-18 (1999)
[Publications] Masumoto N,: "V-src induces cisplatin resistance by increasing the repair of cisplatin-DNA interstand crosslinks in human gallbladder adenocarcinoma cells,"Int,J,Cancer. 80. 731-737 (1999)
[Publications] Nagata C.: "Hair dye use and occupational exposure to organic solvents risk factotos for myeldysplastie syndrome."Leukemia Res.. 23. 57-62 (1999)
[Publications] Okuma K.: "Host range of human T-cell leukemia virus type I analyced by a cell fusion-dependent reporter gene activation assay,"Virology. 254. 235-244 (1999)
[Publications] Tanaka Y,: "Association of the interferon-γ receptor variant(Vall 1Met)with systemic lupus erythematosus."Immunogenetics. 49. 266-271 (1999)
[Publications] Takasaki S.: "Elevated serum soluble CD8 kevel in autoimmune hepatitis the effect of corticsteroid therapy,"Hepatology Res,. 15. 52-63 (1999)
[Publications] Horiuchi T.: "An Ncol polymorphism in the human complement component 7(C7)gene."J,Hum,Genet,. 44. 270-271 (1999)
[Publications] Nagafuchi S,: "Establishment of an embrvonic stem (ES)cell line derved frome a non-obese diabetic (NOD)mouse:in vivo differentiation into lymphocytes and potential for germ line"FEBS Lettes. 455. 101-104 (1999)
[Publications] Yamaoka K,: "Selective DNA-binding activity of interleukin-10-stimulated STAT molecules in human monocytes."J,Interferon and Cytokine Res,. 19. 679-685 (1999)
[Publications] Higuchi M,: "Establishment and Characterization of a Fas-Resistant T cell line."Acta Haematol,. 102. 22-30 (1999)
[Publications] Togawa A.: "Progressive impairment of kidneys and reproductive organs in mice lacking Pho GDI α."Oncogene. 18. 5373-5380 (1999)
[Publications] Nakamuraa T.: "A clonicopathological stufy in young pastients with gastric darcinoma"J,Surgical Oncology. 71. 214-219 (1999)
[Publications] Arinobu Y,: "Antagonistic effects of an Alternative splice variant of human IL-4 II-4 δ 2,on IL-4 actuvutues in himan monocytes and B dells."cell.Immunol,. 191. 161-167 (1999)
[Publications] Nakashima H,: "The combination of polymorphisms within interderon-γ receptor (IFN-γR1)and receptor2(IFN-γ R2)associated with the risk of systemic lupus erythematosus (SLE)."FEBS letters. 453. 187-190 (1999)
[Publications] Akahoshi M,: "Th1/Th2 balance of the peripheral helper T(Th)cells in systemic erythematosus."Arthritis Rheumatism. 42. 1644-1648 (1999)
[Publications] Gao PS.: "Nonpathogenic common variants of IFNγR1 and IFNγR2 in association with total serum IgE levels,"Biochem Biophys Res Commun. 263. 425-429 (1999)
[Publications] Nakashima H,: "Two polymorphisms within interleukin-3(hIL3)gene detected by mismatch PCR/RFLP."Gene and Immunity. 1. 156-158 (1999)
[Publications] Nakashima H,: "Polymorphisms within the I1-10 receptor cDNA gene (IL-10R)in Japanese patients with systemic Iupus erythematosus(SLE)"Rheumatology. 38. 1142-1144 (1999)
[Publications] Nemoto Y.: "Differential of interleukin-4 and interleukin-10 on nitric oxide production by murine macrophages,"Inflammation Res.. 48. 643-650 (1999)

1999 Fiscal Year Annual Research Report

顆粒球造血の細胞内情報伝達機構の解明

Principal Investigator

仁保 喜之 九州大学, 大学院・医学系研究科, 教授 (60091287)

Research Products

[Publications] Niho Y,: "Mokecular Biology Hematological Disorders"Intermal Medicine. 38. 77-78 (1999)

[Publications] Iwasaki H,: "Production of soluble granulocyte colony-stimulating factor receptors from myelomonocytic cells."Mizuno S.. 163. 6907-6911 (1999)

[Publications] Mizuno S.: "Interferon-γ pervents apoptosis Epstein-Barr virus-infected natural kikker cell leukemia in an autocrine fashion,"Blood. 93. 3494-3504 (1999)

[Publications] Stem Cells: "Effect of interleukin 10 on the hematopoietic progenitor cells patients with aplastic anemia."Stem Cells. 17. 147-151 (1999)

[Publications] Uchida N,: "Differential gene expression of human telomerase-associated protein hTERT and TEP in human hematopietic cells."Leuk Res. 23. 1127-1132 (1999)

[Publications] Okuma K.: "Idenfication of a nobel bovine protein which in involved in human T-cell leukemia virus type I(HTLV-1)-induced syncytium for formation."Arch Virol. 144. 1-18 (1999)

[Publications] Masumoto N,: "V-src induces cisplatin resistance by increasing the repair of cisplatin-DNA interstand crosslinks in human gallbladder adenocarcinoma cells,"Int,J,Cancer. 80. 731-737 (1999)

[Publications] Nagata C.: "Hair dye use and occupational exposure to organic solvents risk factotos for myeldysplastie syndrome."Leukemia Res.. 23. 57-62 (1999)

[Publications] Okuma K.: "Host range of human T-cell leukemia virus type I analyced by a cell fusion-dependent reporter gene activation assay,"Virology. 254. 235-244 (1999)

[Publications] Tanaka Y,: "Association of the interferon-γ receptor variant(Vall 1Met)with systemic lupus erythematosus."Immunogenetics. 49. 266-271 (1999)

[Publications] Takasaki S.: "Elevated serum soluble CD8 kevel in autoimmune hepatitis the effect of corticsteroid therapy,"Hepatology Res,. 15. 52-63 (1999)

[Publications] Horiuchi T.: "An Ncol polymorphism in the human complement component 7(C7)gene."J,Hum,Genet,. 44. 270-271 (1999)

[Publications] Nagafuchi S,: "Establishment of an embrvonic stem (ES)cell line derved frome a non-obese diabetic (NOD)mouse:in vivo differentiation into lymphocytes and potential for germ line"FEBS Lettes. 455. 101-104 (1999)

[Publications] Yamaoka K,: "Selective DNA-binding activity of interleukin-10-stimulated STAT molecules in human monocytes."J,Interferon and Cytokine Res,. 19. 679-685 (1999)

[Publications] Higuchi M,: "Establishment and Characterization of a Fas-Resistant T cell line."Acta Haematol,. 102. 22-30 (1999)

[Publications] Togawa A.: "Progressive impairment of kidneys and reproductive organs in mice lacking Pho GDI α."Oncogene. 18. 5373-5380 (1999)

[Publications] Nakamuraa T.: "A clonicopathological stufy in young pastients with gastric darcinoma"J,Surgical Oncology. 71. 214-219 (1999)

[Publications] Arinobu Y,: "Antagonistic effects of an Alternative splice variant of human IL-4 II-4 δ 2,on IL-4 actuvutues in himan monocytes and B dells."cell.Immunol,. 191. 161-167 (1999)

[Publications] Nakashima H,: "The combination of polymorphisms within interderon-γ receptor (IFN-γR1)and receptor2(IFN-γ R2)associated with the risk of systemic lupus erythematosus (SLE)."FEBS letters. 453. 187-190 (1999)

[Publications] Akahoshi M,: "Th1/Th2 balance of the peripheral helper T(Th)cells in systemic erythematosus."Arthritis Rheumatism. 42. 1644-1648 (1999)

[Publications] Gao PS.: "Nonpathogenic common variants of IFNγR1 and IFNγR2 in association with total serum IgE levels,"Biochem Biophys Res Commun. 263. 425-429 (1999)

[Publications] Nakashima H,: "Two polymorphisms within interleukin-3(hIL3)gene detected by mismatch PCR/RFLP."Gene and Immunity. 1. 156-158 (1999)

[Publications] Nakashima H,: "Polymorphisms within the I1-10 receptor cDNA gene (IL-10R)in Japanese patients with systemic Iupus erythematosus(SLE)"Rheumatology. 38. 1142-1144 (1999)

[Publications] Nemoto Y.: "Differential of interleukin-4 and interleukin-10 on nitric oxide production by murine macrophages,"Inflammation Res.. 48. 643-650 (1999)

仁保喜之九州大学, 大学院・医学系研究科, 教授 (60091287)