2000 Fiscal Year Annual Research Report

ヒト型ケモカイン遺伝子ノックインマウスの作製

Research Project

Project/Area Number	11680818
Research Institution	The University of Tokyo
Principal Investigator	須藤カツ子東京大学, 医科学研究所, 教務職員 (50126091)
Co-Investigator(Kenkyū-buntansha)	柴田進和日本学術振興会, 特別研究員(PD) 浅野雅秀金沢大学, 医学部, 教授 (50251450) 岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)
Keywords	ケモカイン / SDF-1 / トランスジェニックマウス
Research Abstract	本研究では、ヒト型ケモカイン遺伝子導入マウスの作製を目的として実験を実施している。免疫不全マウスにヒト免疫細胞あるいは免疫系臓器の一部を移植してマウス体内においてヒト免疫系を再現したSCID-huマウスは現在、ヒト造血細胞分化の研究や感染症・白血病などの疾患モデルとして利用されているが、ヒト型ケモカインの遺伝子導入マウスを利用することにより、実際の生体における免疫細胞の動態をより良く再現したモデルとなることが期待される。その中でも、造血幹細胞のホーミングに関わるケモカインのSDF-1は、ヒト造血幹細胞をレシピエントマウスへ移植した際にマウス造血組織にヒト幹細胞を効率的にホーミングさせるために有効に利用できると考えられる。ヒト造血幹細胞のみの移植によってはレシピエントマウス内でヒトTリンパ球発生は認められないが、マウス胸腺微小環境内においてヒト造血幹細胞はTリンパ球系列へと分化・増殖しうることから、移植したヒト造血幹細胞をレシピエントマウス胸腺組織にホーミングさせることによって、ヒトTリンパ球発生を支持しうるマウスの作出が可能であると考えられる。そこで我々はヒト造血幹細胞移植によりヒトTリンパ球発生を支持するレシピエントマウスの作出を目的として、ヒトSDF-1を胸腺において発現するトランスジェニック(Tg)マウス作製を試みた。Tgマウス作製のための供卵マウスとしてはNOD-scidマウスを用いた。胸腺でSDF-1を過剰発現するためにプロモータにはproximallckプロモータを用い、弱いガンマ線照射でSDF-1の発現誘導がかけられるようにデザインした。現在、NOD-scidマウス受精卵前核へのDNAマイクロインジェクションによって、トランスジェニックマウスの作出およびラインの確立を実施中である。

Research Products

(28 results)

All Other

All Publications (28 results)

[Publications] 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)
[Publications] Fukamauchi,F.: "TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus."Biochem.Biphys.Res.Commun.,. 281. 220-226 (2001)
[Publications] Horai,R.: "Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in IL-1 receptor antagonist-deficient mice."J.Exp.Med.. 191. 313-320 (2000)
[Publications] Serizawa,S.: "Mutually exclusive expression of odorant receptor transgenes."Nat.Neurosci.. 3. 687-693 (2000)
[Publications] Uetani,N.: "Impaired learning with enhanced hippocampal long-term potentiation in PTPδ-deficient mice."EMBO J.. 19. 2775-2785 (2000)
[Publications] 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)
[Publications] 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)
[Publications] Tagawa,Y.: "Bimodal role of endogenous interleukin-6 in concanavalin A-induced hepatitis in mice."J.Leukoc.Biol.. 67. 90-96 (2000)
[Publications] Hino,A.: "Interferon γ priming is not critical for IL-12 production of murine spleen cells."Cytokine. 12. 12-20 (2000)
[Publications] 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)
[Publications] 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)
[Publications] Nishihori,H.: "Participation of endogenously produced IFN-γ in interleukin 4-mediated tumor rejection."Human Gene Therapy. 11. 659-668 (2000)
[Publications] Yamaguchi,K.: "Involvement of interleukin-1 in the inflammatory actions of aminobisphosphonates in mice."Br.J.Pharmacol.. 130. 1646-1654 (2000)
[Publications] 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)
[Publications] 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)
[Publications] Yamada,H.: "Protective role of interleukin-1 in mycobacterial infection in IL-1 α/βdouble-knockout mice."Lab.Invest.. 80. 759-767 (2000)
[Publications] Ohkusu,K.: "Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania major infection."Infect.Immun.. 68. 2449-2456 (2000)
[Publications] 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)
[Publications] Kido,M.: "Presence of a higher molecular weigh β-1,4-galactosyltransferase in mouse liver."Acta Histochem.Cytochem.. 33. 215-221 (2000)
[Publications] Igarashi,I.: "Immunization with recombinant surface antigens p26 with Freund's adjuvants against Babesia rodhaini infection."J.Vet.Med.Sci.. 62. 717-723 (2000)
[Publications] Miura,T.: "Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria monocytogenes infection."FEMS Immunol.Med.Microbiol.. 28. 335-341 (2000)
[Publications] Mun,H.-S.: "Toxoplasma gondii Hsp70 as a danger signal in Toxoplasma gondii-infected mice."Cell Stress & Chaperones. 5. 328-335 (2000)
[Publications] Sugawara,I.: "IL-4 is required for defense against Mycobacterial infection."Microbiol.Immunol.. 44. 971-979 (2000)
[Publications] 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).
[Publications] 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).
[Publications] Seino,K.: "Requirement for NKT cells in the induction of allograft tolerance."Proc.Natl.Acad.U.S.A.. (in press).
[Publications] Naruse-Nakajima,C.: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1."Mechanisms of Development. (in press).
[Publications] 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 Fiscal Year Annual Research Report

ヒト型ケモカイン遺伝子ノックインマウスの作製

Principal Investigator

須藤 カツ子 東京大学, 医科学研究所, 教務職員 (50126091)

Research Products

[Publications] 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)

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

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] Tagawa,Y.: "Bimodal role of endogenous interleukin-6 in concanavalin A-induced hepatitis in mice."J.Leukoc.Biol.. 67. 90-96 (2000)

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

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

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

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

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

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

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

[Publications] 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).

[Publications] 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).

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

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

[Publications] 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).

須藤カツ子東京大学, 医科学研究所, 教務職員 (50126091)