1999 年度実績報告書

発生工学的手法を用いた関節リウマチモデルの開発

研究課題

研究課題/領域番号	10558120
研究機関	東京大学
研究代表者	岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)
研究分担者	須藤カツ子東京大学, 医科学研究所, 教務職員 (50126091) 安田二郎東京大学, 医科学研究所, 助手 (10282518) 浅野雅秀金沢大学, 医学部, 教授 (50251450) 上田進財団法人日本生物科学研究所, 所長(研究職)
キーワード	関節リウマチ / トランスジェニックマウス / ノックアウトマウス / 疾患モデル / サイトカイン / HTLV-I
研究概要	疾患モデルとしての有用性は、病態の再現性・忠実度と、病態や発症機構に関する基礎研究の裏付けによって決まる。我々は、これまでHTLV-I-Tgマウスが関節炎のモデルマウスとして有用であることを示してきたが、本年はさらに詳細な検討を行う目的で、HTLV-Iのtax遺伝子をT細胞あるいはマクロファージ系の細胞に特異的に発現させ、それぞれのTgマウスの表現型の検討を行った。まず、T細胞特異的tax-Tgマウスを作製するためにCD4プロモーター、マクロファージ特異的tax-Tgマウスを作製するためにc-fmsプロモーターを使用し、Tgマウス作製した。その結果、CD4-tax-Tgでは、導入遺伝子の発現がT細胞とマクロファージで認められ、関節炎と全身性の自己免疫症状が認められた。一方、fms-tax-Tgマウスでは、マクロファージで発現が認められ、関節炎を発症することが明らかになった。現在は、さらに詳細な検討を行いそれぞれのマウスで自己免疫を誘導する細胞種の同定を行う予定である。

研究成果

(13件)

すべてその他

すべて文献書誌 (13件)

[文献書誌] Horai,R.: "Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in IL-1 receptor antagonist-deficient mice"J.Exp.Med.. 191. 313-320 (2000)
[文献書誌] Kotani,M.: "Involvement of autoimmunity against type II collagen in the development of arthritis in mice transgenic for the human T cell leukemia virus type I tax gene"Eur.J.Immunol.. 29. 54-64 (1999)
[文献書誌] Saijo,S.: "Bone marrow derived cells are responsible for the development of auto-immune arthritis in HTLV-I transgenic mice and those of normal mice can suppress the disease"J.Immunol.. 163. 5700-5707 (1999)
[文献書誌] Habu,K.: "The HTLV-I-tax gene is responsible for the development of both inflammatory polyarthropathy resembling rtheumatoid arthritis and non-inflammatory ankylotic arthropathy in transgenic mice"J.Immunol.. 162. 2956-2963 (1999)
[文献書誌] Shimada,S.: "Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA"J.Immunol.. 163. 5367-5373 (1999)
[文献書誌] Hyodo,Y.: "Interleukin 18 upregulates perforin-mediated NK activity without increasing perforin mRNA expression by binding to constitutively expressed IL-18R"J.Immunol.. 162. 1662-1668 (1999)
[文献書誌] Tsuji,H.: "Alleviation of lipopolysaccharide-induced acute liver injury in Propionibacterium acnes-primed interferonγ deficient mice with a concomitant reduction of tumor necrosis factor-α,interleukin-12 and interleukin-18 production"J.Immunol.. 162. 1049-1055 (1999)
[文献書誌] Igarashi,I: "Roles of CD4+ T cells and IFN-γ in protective immunity against Babesia microti infection in mice"Infection and Immunity. 67. 4143-4148 (1999)
[文献書誌] Kobayashi,M: "Toxoplasma gondii : difference of invasion into tissue of digestive organs between susceptible and resistant strain and influence of IFN-γ in mice inoculated with the cyst per orally"J.Parasitology. 85. 973-975 (1999)
[文献書誌] Sawai,N.: "The role of interferon-γ in Helicobacter pylori-induced gastric inflammatory responses in a mouse model"Infection and Immunity. 67. 279-285 (1999)
[文献書誌] Kawakami,K: "Induction of lymphcytic inflammatory changes in the lung interstitium by human T lymphotropic virus type I"Am.J.Respir.Crit.Care Med. 160. 995-1000 (1999)
[文献書誌] Tagawa,Y.: "Bimodal role of endogenous interleukin-6 in concanavalin A-induced hepatitis in mice"J.Leukocyte Biology. 67. 90-96 (2000)
[文献書誌] Hino,A.: "Interferon-γ priming is not critical for IL-12 production of murine spleen cells"Cytokine. 12. 12-20 (2000)

1999 年度 実績報告書

発生工学的手法を用いた関節リウマチモデルの開発

研究代表者

岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)

研究成果

[文献書誌] Horai,R.: "Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in IL-1 receptor antagonist-deficient mice"J.Exp.Med.. 191. 313-320 (2000)

[文献書誌] Kotani,M.: "Involvement of autoimmunity against type II collagen in the development of arthritis in mice transgenic for the human T cell leukemia virus type I tax gene"Eur.J.Immunol.. 29. 54-64 (1999)

[文献書誌] Saijo,S.: "Bone marrow derived cells are responsible for the development of auto-immune arthritis in HTLV-I transgenic mice and those of normal mice can suppress the disease"J.Immunol.. 163. 5700-5707 (1999)

[文献書誌] Habu,K.: "The HTLV-I-tax gene is responsible for the development of both inflammatory polyarthropathy resembling rtheumatoid arthritis and non-inflammatory ankylotic arthropathy in transgenic mice"J.Immunol.. 162. 2956-2963 (1999)

[文献書誌] Shimada,S.: "Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA"J.Immunol.. 163. 5367-5373 (1999)

[文献書誌] Hyodo,Y.: "Interleukin 18 upregulates perforin-mediated NK activity without increasing perforin mRNA expression by binding to constitutively expressed IL-18R"J.Immunol.. 162. 1662-1668 (1999)

[文献書誌] Tsuji,H.: "Alleviation of lipopolysaccharide-induced acute liver injury in Propionibacterium acnes-primed interferonγ deficient mice with a concomitant reduction of tumor necrosis factor-α,interleukin-12 and interleukin-18 production"J.Immunol.. 162. 1049-1055 (1999)

[文献書誌] Igarashi,I: "Roles of CD4+ T cells and IFN-γ in protective immunity against Babesia microti infection in mice"Infection and Immunity. 67. 4143-4148 (1999)

[文献書誌] Kobayashi,M: "Toxoplasma gondii : difference of invasion into tissue of digestive organs between susceptible and resistant strain and influence of IFN-γ in mice inoculated with the cyst per orally"J.Parasitology. 85. 973-975 (1999)

[文献書誌] Sawai,N.: "The role of interferon-γ in Helicobacter pylori-induced gastric inflammatory responses in a mouse model"Infection and Immunity. 67. 279-285 (1999)

[文献書誌] Kawakami,K: "Induction of lymphcytic inflammatory changes in the lung interstitium by human T lymphotropic virus type I"Am.J.Respir.Crit.Care Med. 160. 995-1000 (1999)

[文献書誌] Tagawa,Y.: "Bimodal role of endogenous interleukin-6 in concanavalin A-induced hepatitis in mice"J.Leukocyte Biology. 67. 90-96 (2000)

[文献書誌] Hino,A.: "Interferon-γ priming is not critical for IL-12 production of murine spleen cells"Cytokine. 12. 12-20 (2000)

1999 年度実績報告書

岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)