2000 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	上田進 (財)日本生物科学研究所, 所長(研究職) 須藤カツ子東京大学, 医科学研究所, 教務職員 (50126091)
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 / HTLV-I / IL-1 / IL-6 / 自己免疫 / 病態モデルマウス
研究概要	疾患モデルとしての有用性は、病態の再現性・忠実性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を行った。まず、T細胞特異的な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マウスを作製した。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、2ヶ月齢でほぼ100%のマウスが関節炎を発症することが明らかとなった。また、fms-tax-Tgの骨髄細胞を野生型マウスに移植することによる関節炎の誘導に成功した。この結果から、関節滑膜細胞の骨髄由来細胞の異常が関節炎の原因であることが示唆された。さらに、従来のHTLV-I-Tgのみならず、c-fms-tax-Tgが関節炎モデルマウスとして有用であることが示された。

研究成果

(28件)

すべてその他

すべて文献書誌 (28件)

[文献書誌] Hayakawa,Y.: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells."Nat Med.. 7. 94-100 (2001)
[文献書誌] Fukamauchi,F.: "TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus."Biochem.Biphys.Res.Commun.,. 281. 220-226 (2001)
[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] Serizawa,S.: "Mutually exclusive expression of odorant receptor transgenes."Nat.Neurosci.. 3. 687-693 (2000)
[文献書誌] Uetani,N.: "Impaired learning with enhanced hippocampal long-term potentiation in PTPδ-deficient mice."EMBO J.. 19. 2775-2785 (2000)
[文献書誌] Tanaka,J.: "Lipopolysaccharide-induced HIV-1 expression in transgenic mice is mediated by tumor necrosis factor-alpha and interleukin-1, but not by interferon-gamma nor interleukin-6."AIDS. 14. 1299-1307 (2000)
[文献書誌] Hayashi,K.: "Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells."J.Immunol.. 165. 6816-6824 (2000)
[文献書誌] Tagawa,Y.: "Bimodal role of endogenous interleukin-6 in concanavalin A-induced hepatitis in mice."J.Leukoc.Biol.. 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)
[文献書誌] Miyazato,A.: "Chemokine synthesis and cellular inflammatory changes in lungs of mice bearing p40tax of human T-lymphotropic virus type 1."Clin.Exp.Immunol.. 120. 113-124 (2000)
[文献書誌] Takikawa,O.: "Interferon-γ-dependent/independent expression of indoleamine 2,3-dioxygenase. Studies with interferon-γ-knockout mice."Adv.Exp.Med.Biol.. 467. 553-557 (2000)
[文献書誌] Nishihori,H.: "Participation of endogenously produced IFN-γ in interleukin 4-mediated tumor rejection."Human Gene Therapy. 11. 659-668 (2000)
[文献書誌] Yamaguchi,K.: "Involvement of interleukin-1 in the inflammatory actions of aminobisphosphonates in mice."Br.J.Pharmacol.. 130. 1646-1654 (2000)
[文献書誌] Ohta,A.: "Indispensable role for TNF-α and IFN-γ at the effector phase of liver injury mediated by Th1 cells specific to hepatitis B virus surface antigen."J.Immunol.. 165. 956-961 (2000)
[文献書誌] Kawakami,K.: "IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-γ production by NK cells."J.Immunol.. 165. 941-947 (2000)
[文献書誌] Yamada,H.: "Protective role of interleukin-1 in mycobacterial infection in IL-1 α/β double-knockout mice."Lab.Invest.. 80. 759-767 (2000)
[文献書誌] Ohkusu,K.: "Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania major infection."Infect.Immun.. 68. 2449-2456 (2000)
[文献書誌] Sasaki,S.: "Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon."Infect.Immun.. 68. 2424-2430 (2000)
[文献書誌] Kido,M.: "Presence of a higher molecular weight β-1,4-galactosyltransferase in mouse liver."Acta Histochem.Cytochem.. 33. 215-221 (2000)
[文献書誌] Igarashi,I.: "Immunization with recombinant surface antigens p26 with Freund's adjuvants against Babesia rodhaini infection."J.Vet.Med.Sci.. 62. 717-723 (2000)
[文献書誌] Miura,T.: "Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria monocytogenes infection."FEMS Immunol.Med.Microbiol.. 28. 335-341 (2000)
[文献書誌] Mun,H.-S.: "Toxoplasma gondii Hsp70 as a danger signal in Toxoplasma gondii-infected mice."Cell Stress & Chaperones. 5. 328-335 (2000)
[文献書誌] Sugawara,I.: "IL-4 is required for defense against Mycobacterial infection."Microbiol.Immunol.. 44. 971-979 (2000)
[文献書誌] Morita,Y.: "Caspase-2 deficiency rescues female germ cells from death due to cytokine insufficiency but not meiotic defects caused by Ataxia Telangiectasia-mutated (Atm) gene inactivation."Endocrinology. (in press).
[文献書誌] Ishii,T.: "Projection of three subsets of olfactory neurons expressing the odorant receptor transgene and the two cognate endogenous alleles."Genes to Cells,. (in press).
[文献書誌] Seino,K.: "Requirement for NKT cells in the induction of allograft tolerance."Proc.Natl.Acad.U.S.A.,. (in press).
[文献書誌] Naruse-Nakajima,C.: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1."Mechanisms of Development,. (in press).
[文献書誌] Yoneto,T.: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage plasmodium berghei XAT infection."J.Immunol.. (in press).

2000 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] Hayakawa,Y.: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells."Nat Med.. 7. 94-100 (2001)

[文献書誌] Fukamauchi,F.: "TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus."Biochem.Biphys.Res.Commun.,. 281. 220-226 (2001)

[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] Serizawa,S.: "Mutually exclusive expression of odorant receptor transgenes."Nat.Neurosci.. 3. 687-693 (2000)

[文献書誌] Uetani,N.: "Impaired learning with enhanced hippocampal long-term potentiation in PTPδ-deficient mice."EMBO J.. 19. 2775-2785 (2000)

[文献書誌] Tanaka,J.: "Lipopolysaccharide-induced HIV-1 expression in transgenic mice is mediated by tumor necrosis factor-alpha and interleukin-1, but not by interferon-gamma nor interleukin-6."AIDS. 14. 1299-1307 (2000)

[文献書誌] Hayashi,K.: "Diminution of the AML1 transcription factor function causes differential effects on the fates of CD4 and CD8 single-positive T cells."J.Immunol.. 165. 6816-6824 (2000)

[文献書誌] Tagawa,Y.: "Bimodal role of endogenous interleukin-6 in concanavalin A-induced hepatitis in mice."J.Leukoc.Biol.. 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)

[文献書誌] Miyazato,A.: "Chemokine synthesis and cellular inflammatory changes in lungs of mice bearing p40tax of human T-lymphotropic virus type 1."Clin.Exp.Immunol.. 120. 113-124 (2000)

[文献書誌] Takikawa,O.: "Interferon-γ-dependent/independent expression of indoleamine 2,3-dioxygenase. Studies with interferon-γ-knockout mice."Adv.Exp.Med.Biol.. 467. 553-557 (2000)

[文献書誌] Nishihori,H.: "Participation of endogenously produced IFN-γ in interleukin 4-mediated tumor rejection."Human Gene Therapy. 11. 659-668 (2000)

[文献書誌] Yamaguchi,K.: "Involvement of interleukin-1 in the inflammatory actions of aminobisphosphonates in mice."Br.J.Pharmacol.. 130. 1646-1654 (2000)

[文献書誌] Ohta,A.: "Indispensable role for TNF-α and IFN-γ at the effector phase of liver injury mediated by Th1 cells specific to hepatitis B virus surface antigen."J.Immunol.. 165. 956-961 (2000)

[文献書誌] Kawakami,K.: "IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-γ production by NK cells."J.Immunol.. 165. 941-947 (2000)

[文献書誌] Yamada,H.: "Protective role of interleukin-1 in mycobacterial infection in IL-1 α/β double-knockout mice."Lab.Invest.. 80. 759-767 (2000)

[文献書誌] Ohkusu,K.: "Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania major infection."Infect.Immun.. 68. 2449-2456 (2000)

[文献書誌] Sasaki,S.: "Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon."Infect.Immun.. 68. 2424-2430 (2000)

[文献書誌] Kido,M.: "Presence of a higher molecular weight β-1,4-galactosyltransferase in mouse liver."Acta Histochem.Cytochem.. 33. 215-221 (2000)

[文献書誌] Igarashi,I.: "Immunization with recombinant surface antigens p26 with Freund's adjuvants against Babesia rodhaini infection."J.Vet.Med.Sci.. 62. 717-723 (2000)

[文献書誌] Miura,T.: "Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria monocytogenes infection."FEMS Immunol.Med.Microbiol.. 28. 335-341 (2000)

[文献書誌] Mun,H.-S.: "Toxoplasma gondii Hsp70 as a danger signal in Toxoplasma gondii-infected mice."Cell Stress & Chaperones. 5. 328-335 (2000)

[文献書誌] Sugawara,I.: "IL-4 is required for defense against Mycobacterial infection."Microbiol.Immunol.. 44. 971-979 (2000)

[文献書誌] Morita,Y.: "Caspase-2 deficiency rescues female germ cells from death due to cytokine insufficiency but not meiotic defects caused by Ataxia Telangiectasia-mutated (Atm) gene inactivation."Endocrinology. (in press).

[文献書誌] Ishii,T.: "Projection of three subsets of olfactory neurons expressing the odorant receptor transgene and the two cognate endogenous alleles."Genes to Cells,. (in press).

[文献書誌] Seino,K.: "Requirement for NKT cells in the induction of allograft tolerance."Proc.Natl.Acad.U.S.A.,. (in press).

[文献書誌] Naruse-Nakajima,C.: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1."Mechanisms of Development,. (in press).

[文献書誌] Yoneto,T.: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage plasmodium berghei XAT infection."J.Immunol.. (in press).

2000 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)