1998 Fiscal Year Annual Research Report

サイトカイン研究のための遺伝子改変マウスライブラリーの作製

Research Project

Project/Area Number	08408037
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)	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) 松澤昭雄東京大学, 医科学研究所, 教授 (50012745)
Keywords	ノックアウトマウス / IL-1α / IL-1β / IL-1レセプターアンタゴニスト / IFN-γ / IL-6 / HTLV-L Tgマウス / HIV-Tgマウス
Research Abstract	これまでに作製したIFN-γ、IL-1α、IL-1β、IL-1α/βダブル、IL-1レセプターアンタゴニスト(RA)および他の研究者より入手したIL-6、IL4、それぞれのノックアウト(KO)マウスについて昨年度に引き続きBALB/cA、C57BL/6JおよびDBA/1Jマウスに戻し交配を行った。現在BALB/cAとC57BL/6Jについては全ての系統で8世代まで進み、兄妹交配によりホモ接合体を得た。現在は8世代のホモ接合体の受精卵の凍結保存を進めると共に、他の研究者に対する分与を行っている。それぞれのマウスにおける表現型を解析したところ、チオグリコレート誘導腹腔マクロファージでは、LPS刺激によるIL-1aの発現誘導は、L-1βKOマウスでは野生型マウスに比較し有意に低く、また、IL-1αのKOマウスではIL-1βの発現誘導が有意に低くなっていることがわかり、L-1αとIL-1βではお互いに発現を制御している可能性が示唆された。さらに、IL-1β、IL-1α/βダブルKOマウスではテレピン油投与時の体温の上昇が野生型マウスと比較し、強く抑えられ、IL-1RAKOマウスでは野生型マウスよりさらに高温になることがわかった。さらに、この時の血中のコルチコステロン濃度はIL-1α/βダブルKOマウスで有意に低下していた。これらの結果からIL-1は生体の恒常性の維持に深く関わっていることが示された。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Horai, R,.et al.: "Production of mice deficient in genes for IL-1α, IL-1β, IL-1α/β, and IL-1ra shous 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 madiliot by Frsantrgen" J.Immunol.161. 6592-6598 (1998)
[Publications] Kotani, M.et al: "Involvement of Autoimmunity. Against type II collgen in the development of arthritis in mice transgenic for the HTLV-I tax gene." Eur.J.Immuinol.29. 54-64 (1999)
[Publications] Habu, K., et al: "The HTLV-I-taxgene is responsible for the development of both infrainnatory polyarthropathy and non-inflammatory ankyloticar thropathy in transgenic imce" J.Immunol. (in press).
[Publications] Flamand, V.et al: "CD40 ligation prevents neonatal induction of transplan tation tolerance." J.Immunol. 160. 4666-4669 (1998)
[Publications] Kyuwa, S.et al: "Murine coronaviru s-induced subacute fatal poitonitis in C57346 mice deficient in gamma interferon." J.Virol.72. 9286-9290 (1998)
[Publications] Kyuwa, S.et al: "MHV-induced fatal peritonitis in mice lacking IFV-γ." 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 Fras ligand." Nat Med.4. 1287-1292 (1998)
[Publications] Kido, M.et al: "Presence of polysialic acid and HNK-1 carloohydrate on lorain glycoproteins from β-1, 4 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 Mycobactinum Tuberavosis" J.Med.Microbiol.47. 871-877 (1998)
[Publications] Tagawa, Y.et al.: "lnvolvement of Fas/Fas ligard system-mediated apoptosis in the development of Con A-induced hepatitis." Eur.J.Immunol.28. 4105-4113 (1998)
[Publications] Tsuji, H.et al: "Alleviation of LPS-induced acute liver injury in P.ac nes・primed・IFN′-r-deficient mice by a concomitant reduce on of DVR a, 2L-12 and IL-18 Production" J.Immunol.162. 1049-1055 (1999)
[Publications] Hyodo, Y.et al: "IL-18 upregulates exocytosis-mediated NK activity without uffecting parforin mRNA expression by binding to constitulively expressed IL IFR" J.Immunol.162. 8662-8668 (1999)
[Publications] Sawai,N.et al: "Role of gamma interferon in Hlicobacter pylori-induced gastric inflammatory responses in a mouse model" Infect.Immun.67. 279-285 (1999)

1998 Fiscal Year Annual Research Report

サイトカイン研究のための遺伝子改変マウスライブラリーの作製

Principal Investigator

岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)

Research Products

[Publications] Horai, R,.et al.: "Production of mice deficient in genes for IL-1α, IL-1β, IL-1α/β, and IL-1ra shous 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 madiliot by Frsantrgen" J.Immunol.161. 6592-6598 (1998)

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

[Publications] Habu, K., et al: "The HTLV-I-taxgene is responsible for the development of both infrainnatory polyarthropathy and non-inflammatory ankyloticar thropathy in transgenic imce" J.Immunol. (in press).

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

[Publications] Kyuwa, S.et al: "Murine coronaviru s-induced subacute fatal poitonitis in C57346 mice deficient in gamma interferon." J.Virol.72. 9286-9290 (1998)

[Publications] Kyuwa, S.et al: "MHV-induced fatal peritonitis in mice lacking IFV-γ." 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 Fras ligand." Nat Med.4. 1287-1292 (1998)

[Publications] Kido, M.et al: "Presence of polysialic acid and HNK-1 carloohydrate on lorain glycoproteins from β-1, 4 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 Mycobactinum Tuberavosis" J.Med.Microbiol.47. 871-877 (1998)

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

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

[Publications] Hyodo, Y.et al: "IL-18 upregulates exocytosis-mediated NK activity without uffecting parforin mRNA expression by binding to constitulively expressed IL IFR" J.Immunol.162. 8662-8668 (1999)

[Publications] Sawai,N.et al: "Role of gamma interferon in Hlicobacter pylori-induced 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)