1996 Fiscal Year Annual Research Report

サイトカ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 Category	Grant-in-Aid for Scientific Research (A)
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)	田川陽一東京大学, 医科学研究所, 教務職員 (70262079) 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, 助教授 (50012745)
Keywords	ノックアウトマウス / IL-1α / IL-1β / IFN-γ / IL-1レセプターアンタゴニスト / IL-12 / HTLV-I-Tgマウス / HIV-I-Tgマウス
Research Abstract	これまでにIL-1α、IL-1β、IFN-γについて遺伝子破壊マウス(KOマウス)を作製した。今年度はさらにIL-1α、IL-1βのダブルKOマウスおよびIL-1レセプターアンタゴニスト(IL-1RA)のKOマウスを作製した。また、やはり免疫系における役割が注目されているIL-12についてはキメラマウスを作製し、現在、KO遺伝子の生殖系列への伝達を確認中である。 IL-1α、βのダブルノックアウトは、両遺伝子がきわめて近接しているため、交配により作製することが難しく、ES細胞において両遺伝子が欠損したものを作製した。このため、選択用マーカーとしてネオマイシン耐性およびハイグロマイシン耐性遺伝子を用いた。 IL-1α、IL-1β、IFN-γ、IL-1α/βダブル、IL-1RAそれぞれのKOマウスのホモ接合体は正常に発生し、SPF環境下では健康であった。また、IL-1α、βおよびIL-1α/βダブルKOマウスはLPS投与時の致死率に差は見られなかった。それぞれのKOマウスは人工受精によりC57BL/6、BALB/c、およびDBA/1マウスに戻し交配をし、現在3世代から10世代まで進めた。また、F2世代以上で100個以上の8細胞期胚を凍結保存した。 IL-1β、IFN-γおよびIL-1α/βダブルKOマウスはBALB/cマウスに4世代戻し交配した時点でHTLV-I-Tgマウス、およびHIV-Tgマウスに交配し、サイトカイン遺伝子をホモに欠損したTgマウスを現在作製中である。今後HTLV-I-Tgマウスにおいては、自己免疫に対する影響を、HIV-TgマウスにおいてはLPS刺激によるHIV遺伝子誘導に対する影響を検討する予定である。

Research Products
(20 results)

All Other

All Publications (20 results)

[Publications] Arakawa,H: "Extrachromosomal circular DNAs from differentiating embryonic stem cells" Cell Struc.Funct. (in press). (1997)
[Publications] Asano,M: "Growth retardation and early death of β-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells" EMBO.J.(in press). (1997)
[Publications] Asano,M: "Growth retardation and early death of β-1,4-galactosyltransferase knockout mice with augumented proliteration and abnormal differentiation of epithelial cells" In“Mouse Molecular Genetics". 26 (1996)
[Publications] Fujisawa,K: "Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-I tax transgenic mice" J.Clin.Invest. 98. 271-278 (1996)
[Publications] Kidani,Y: "Orally active DACH-Pt(IV)compounds" IN“Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy". 45-51 (1996)
[Publications] Kizu,R: "An orally active antitumor cyclohexanedimine-Pt(IV)complex:trans,cis,cis-bis(n-valerato)(oxalato)(1R,2R-cyclohexanediamine)PT(IV)" Anti-CancerDrugs. 7. 248-256 (1996)
[Publications] Matsuzawsa,A: "Establishment of tumor dormant state following clinically complete cure of disseminated leukemia by chemotherapy in mice." In“Premalignancy and Tumor Dormancy". 89-103 (1996)
[Publications] Miez,M: "Selective reduction of vα14^+NK cells associated with disease development in autoimmune-prone mice" J.Immunol.156. 4035-4040 (1996)
[Publications] Nakano,H: "Genetic defect in T Iymphocyte-specific homing into peripheral lymph nodes." Eur.J.Immunol. (in press). (1997)
[Publications] Nakano,H: "Deletion of peripheral vβ14^+T cells by Mtv-2-encoded viral superantigen preceded by blastogenesis and DNA synthesis but not by specific expansion." Cell.Immunol.168. 281-290 (1996)
[Publications] Nanbu,H: "Fas-independent apoptosis of photoreceptor cells in C3H mice." Exp.Anim. 45. 309-315 (1996)
[Publications] Oyaizu,T: "Studies on the mechanism of dimethylnitrosamine-induced acute lever inJury in mice" Exp.Toxical.Pathol. (in press). (1997)
[Publications] Saijo,S: "Involvement of autoimmunity in inflammatory arthropathy that developed in HTLV-1 transgenic mice." Eur.Cytokine Netw.7. 606 (1996)
[Publications] Shimizu.M: "Augmentation of antitumor immunity with bacterial superantigen Staphylococcal enterotoxin B-bond tumor cells" Cancer Res.56. 3731-3736 (1996)
[Publications] Suzuki A.: "Involvement of Fas inregression of vaginal epithelia after ovaricetomy and during an estrus cycle." EMBO J.15. 211-215 (1996)
[Publications] Suzuki,A: "Down regulation of Bc1-2 is the first step on Fas-mediated apoptosis of male reproductive tract." Oncogene. 13. 31-37 (1996)
[Publications] Tagawa,Y: "Resistance of interferon-r deficient mice against in a T-cell dependent manner." Eur.Cytokine Netw. 7. 505 (1996)
[Publications] Tanaka,S.: "Genetic regulation of border zone formation in female mastomys(Praoumys coucha)adrenal cortex." J.Heredit.87. 70-74 (1996)
[Publications] Yoshimoto,T: "Deletion of CD4^+T cells by murine mammary tumor virus(FM)superantigen with broad specificity of T cell receptor β-chain variable region," Virology. 223. 387-391 (1996)
[Publications] Yoshimoto,T: "Interleukin-18(IL-18)together with IL-12 inhibits IgE synthesis by induction of IFN-γ Production from activated B cells." Proc.Nat Acad.Sci.USA. (in press). (1997)

1996 Fiscal Year Annual Research Report

サイトカ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] Arakawa,H: "Extrachromosomal circular DNAs from differentiating embryonic stem cells" Cell Struc.Funct. (in press). (1997)

[Publications] Asano,M: "Growth retardation and early death of β-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells" EMBO.J.(in press). (1997)

[Publications] Asano,M: "Growth retardation and early death of β-1,4-galactosyltransferase knockout mice with augumented proliteration and abnormal differentiation of epithelial cells" In“Mouse Molecular Genetics". 26 (1996)

[Publications] Fujisawa,K: "Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-I tax transgenic mice" J.Clin.Invest. 98. 271-278 (1996)

[Publications] Kidani,Y: "Orally active DACH-Pt(IV)compounds" IN“Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy". 45-51 (1996)

[Publications] Kizu,R: "An orally active antitumor cyclohexanedimine-Pt(IV)complex:trans,cis,cis-bis(n-valerato)(oxalato)(1R,2R-cyclohexanediamine)PT(IV)" Anti-CancerDrugs. 7. 248-256 (1996)

[Publications] Matsuzawsa,A: "Establishment of tumor dormant state following clinically complete cure of disseminated leukemia by chemotherapy in mice." In“Premalignancy and Tumor Dormancy". 89-103 (1996)

[Publications] Miez,M: "Selective reduction of vα14^+NK cells associated with disease development in autoimmune-prone mice" J.Immunol.156. 4035-4040 (1996)

[Publications] Nakano,H: "Genetic defect in T Iymphocyte-specific homing into peripheral lymph nodes." Eur.J.Immunol. (in press). (1997)

[Publications] Nakano,H: "Deletion of peripheral vβ14^+T cells by Mtv-2-encoded viral superantigen preceded by blastogenesis and DNA synthesis but not by specific expansion." Cell.Immunol.168. 281-290 (1996)

[Publications] Nanbu,H: "Fas-independent apoptosis of photoreceptor cells in C3H mice." Exp.Anim. 45. 309-315 (1996)

[Publications] Oyaizu,T: "Studies on the mechanism of dimethylnitrosamine-induced acute lever inJury in mice" Exp.Toxical.Pathol. (in press). (1997)

[Publications] Saijo,S: "Involvement of autoimmunity in inflammatory arthropathy that developed in HTLV-1 transgenic mice." Eur.Cytokine Netw.7. 606 (1996)

[Publications] Shimizu.M: "Augmentation of antitumor immunity with bacterial superantigen Staphylococcal enterotoxin B-bond tumor cells" Cancer Res.56. 3731-3736 (1996)

[Publications] Suzuki A.: "Involvement of Fas inregression of vaginal epithelia after ovaricetomy and during an estrus cycle." EMBO J.15. 211-215 (1996)

[Publications] Suzuki,A: "Down regulation of Bc1-2 is the first step on Fas-mediated apoptosis of male reproductive tract." Oncogene. 13. 31-37 (1996)

[Publications] Tagawa,Y: "Resistance of interferon-r deficient mice against in a T-cell dependent manner." Eur.Cytokine Netw. 7. 505 (1996)

[Publications] Tanaka,S.: "Genetic regulation of border zone formation in female mastomys(Praoumys coucha)adrenal cortex." J.Heredit.87. 70-74 (1996)

[Publications] Yoshimoto,T: "Deletion of CD4^+T cells by murine mammary tumor virus(FM)superantigen with broad specificity of T cell receptor β-chain variable region," Virology. 223. 387-391 (1996)

[Publications] Yoshimoto,T: "Interleukin-18(IL-18)together with IL-12 inhibits IgE synthesis by induction of IFN-γ Production from activated B cells." Proc.Nat Acad.Sci.USA. (in press). (1997)

岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)