1998 Fiscal Year Annual Research Report

発生工学的手法を用いた関節リウマチモデルの作製

Research Project

Project/Area Number	10558120
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	The University of Tokyo
Principal Investigator	岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)
Co-Investigator(Kenkyū-buntansha)	安田二朗東京大学, 医科学研究所, 助手 (10282518) 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) 浅野雅秀東京大学, 医科学研究所, 助手 (50251450)
Keywords	HTLV-I-Tgマウス / コンジェニック / IL-1 / IL-1レセプターアンタゴニスト / 関節リウマチ
Research Abstract	我々は以前より発生工学的手法を用いた疾患モデルを作製することに取組んできたが、その中で、HTLV-I遺伝子を導入したトランスジェニックマウスを作製して、このマウスがヒトの関節リウマチに良く似た慢性関節炎を多発することを発見した。さらにその後の疫学調査でもわが国で、3万人程度がこのウイルスによって関節リウマチを発症している可能性が示された。そこで本研究は、関節リウマチの原因となっている可能性の高いHTLV-Iのトランスジェニックマウスを用いて、自己免疫、関節炎の病態、発症機構を解析し、関節リウマチとの類似性をより明確にすると共に、このマウスを規格系統化して実験動物化することを試みることを目的とする。また、発症に関与すると考えられるIL-1などの遺伝子のノックアウトマウスやトランスジェニックマウスを作製したがこのうち、IL-1トランスジェニックマウスやIL-1レセプターアンタゴニストノックアウトマウスでは自己免疫を発症することがわかってきた。そこでこれらのマウスについても発症機構を解析すると共に実験動物物化を目的とし、BALA/cA、C57BL/6Jなどに戻し交配を行った。現在HTLV-I-Tgマウスは12世代までBALB/cマウスに戻し交配を行ったが、18世代まで進めた後兄妹交配を行う予定である。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Horii,R.et al.: "Production of mice deficient in genes for IL-1α,IL-1β,IL-1α/β,and IL-1 rashows that IL-1β is cruciao in turpentine-induced fever development" J.Exp.Med.187. 1463-1475 (1998)
[Publications] Iwakura,Y.,et al: "The development of autoimmure arthropathy in mice transgenio for the HTLV-I env-pX region is not dependent on H-2 haplotypes and medilied by Fasuatigen" J.Immunol.161. 6592-6598 (1998)
[Publications] Kotani,M.et al.: "Involvement of Autoimmunity Against typeII collgen in the development of arthritisin mice transgenic for the HTLV-I tax gene" Eur.J.Immunol.29. 54-64 (1999)
[Publications] Habu,K.,et al: "The HTLVI-taxgene is responsible for the development of both inflomna-tory pelyarthropathy and non-inflammatory ankyloticarthropathy in trans sentic mice" J.Immunol.in press.
[Publications] Flamand,V.et al: "CD40 ligation prevents neonatal induction of transplantation tolerance" J.Immunol. 160. 4666-4669 (1998)
[Publications] Kyuwa,S.et al: "Murine coronavirus-indeuced subucate fatal poritonitis in C573L/6 mice deficient in gamma interferon" J.Virol.72. 9286-9290 (1998)
[Publications] Kyuwa,S.et al: "MHV-induced fatal peritonitis in mice lacking IFW-T." AdV.Exp.Med.Biol.440. 445-450 (1998)
[Publications] Miwa,K.et al.: "Caspasel-independent IL-1β release and inflammation induced by the apoptosis inducer Fas ligand." Nat.Med.4. 1287-1292 (1998)
[Publications] Kido,M.et al: "Presence of polysialic acid and HNK-1 carbohydrate on brain glycoproteins from β-L4 gal T-krockout mice" Biochem.Biophys.Res.Commun. 245. 860-864 (1998)
[Publications] Sugawara,I.et al: "Induction of granulomas in interferon-γ gene-disrupted nice by aviralent but not by virulent strain of Mycopacterium tuberonlosis" J.Med.Microbiol.47. 871-877 (1998)
[Publications] Tagawa,Y.,et al.: "Involvement of Fas/Fas ligand system-mediated apoptosis in the development of ConA-induced hepatitis." Eur.J.Immunol.28. 4105-4113 (1998)
[Publications] Tsuji,H.et al.: "Alleviation of LPS-induced acute liver injury in P asnes primed IFN-γ-deficient mice by a concomitant reduce on of WFα,2L-12 and IL-18 production." J.Immunol.162. 1049-1055 (1999)
[Publications] Hyodo,Y.et al.: "IL-18 upregulates exocytosis-mediated NK activity withoutuffecting perforin mRNA expression by binding to constitulibely expressed IL 18R." J.Immunol. 162. 8662-8668 (1999)
[Publications] Sawai,N.et al: "Role of gammainterferon in Hlicobacter pylori-irduced gastric inflammatory responses in a mouse model" Infect.Immun.67. 279-285 (1999)

1998 Fiscal Year Annual Research Report

発生工学的手法を用いた関節リウマチモデルの作製

Principal Investigator

岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)

Research Products

[Publications] Horii,R.et al.: "Production of mice deficient in genes for IL-1α,IL-1β,IL-1α/β,and IL-1 rashows that IL-1β is cruciao in turpentine-induced fever development" J.Exp.Med.187. 1463-1475 (1998)

[Publications] Iwakura,Y.,et al: "The development of autoimmure arthropathy in mice transgenio for the HTLV-I env-pX region is not dependent on H-2 haplotypes and medilied by Fasuatigen" J.Immunol.161. 6592-6598 (1998)

[Publications] Kotani,M.et al.: "Involvement of Autoimmunity Against typeII collgen in the development of arthritisin mice transgenic for the HTLV-I tax gene" Eur.J.Immunol.29. 54-64 (1999)

[Publications] Habu,K.,et al: "The HTLVI-taxgene is responsible for the development of both inflomna-tory pelyarthropathy and non-inflammatory ankyloticarthropathy in trans sentic mice" J.Immunol.in press.

[Publications] Flamand,V.et al: "CD40 ligation prevents neonatal induction of transplantation tolerance" J.Immunol. 160. 4666-4669 (1998)

[Publications] Kyuwa,S.et al: "Murine coronavirus-indeuced subucate fatal poritonitis in C573L/6 mice deficient in gamma interferon" J.Virol.72. 9286-9290 (1998)

[Publications] Kyuwa,S.et al: "MHV-induced fatal peritonitis in mice lacking IFW-T." AdV.Exp.Med.Biol.440. 445-450 (1998)

[Publications] Miwa,K.et al.: "Caspasel-independent IL-1β release and inflammation induced by the apoptosis inducer Fas ligand." Nat.Med.4. 1287-1292 (1998)

[Publications] Kido,M.et al: "Presence of polysialic acid and HNK-1 carbohydrate on brain glycoproteins from β-L4 gal T-krockout mice" Biochem.Biophys.Res.Commun. 245. 860-864 (1998)

[Publications] Sugawara,I.et al: "Induction of granulomas in interferon-γ gene-disrupted nice by aviralent but not by virulent strain of Mycopacterium tuberonlosis" J.Med.Microbiol.47. 871-877 (1998)

[Publications] Tagawa,Y.,et al.: "Involvement of Fas/Fas ligand system-mediated apoptosis in the development of ConA-induced hepatitis." Eur.J.Immunol.28. 4105-4113 (1998)

[Publications] Tsuji,H.et al.: "Alleviation of LPS-induced acute liver injury in P asnes primed IFN-γ-deficient mice by a concomitant reduce on of WFα,2L-12 and IL-18 production." J.Immunol.162. 1049-1055 (1999)

[Publications] Hyodo,Y.et al.: "IL-18 upregulates exocytosis-mediated NK activity withoutuffecting perforin mRNA expression by binding to constitulibely expressed IL 18R." J.Immunol. 162. 8662-8668 (1999)

[Publications] Sawai,N.et al: "Role of gammainterferon in Hlicobacter pylori-irduced gastric inflammatory responses in a mouse model" Infect.Immun.67. 279-285 (1999)

岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)