2002 年度実績報告書

各種近交系由来ES細胞の樹立

研究課題

研究課題/領域番号	13680908
研究機関	東京大学
研究代表者	須藤カツ子東京大学, 医科学研究所, 助手 (50126091)
研究分担者	角田茂東京大学, 医科学研究所, 助手 (80345032) 岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)
キーワード	ES細胞 / ノックアウト / 遺伝子改変動物 / キメラマウス
研究概要	現在使用されているES細胞のほとんどは免疫学的、神経科学的あるいは発生学的なデータの少ない129系統マウス由来のものである。そのため多くの場合、遺伝的背景が異なり、あらゆる情報の整った近交系マウスに2年近い歳月を費やしてバッククロスをしている。そこで、遺伝子改変マウス作出時から遺伝的背景のしっかりした近交系マウス由来のES細胞を用いることができればあらゆる点で有利である。しかし、取り扱いが容易であり、多くの遺伝子改変動物を生み出した実績のある129系統由来のES細胞を使用した場合でも、短期バッククロスの方法が取り入れられれば、129系統由来ES細胞の不利な点を解消することができる。そこで、その改善方法を検討している。我々がすでに樹立しているES細胞のうち、BALB/c系統由来ES細胞(ST/c)について、その性状を確認し、生殖系列系であることが確認されている細胞を用いて遺伝子改変マウスの作出を試みキメラマウスの作出に成功した。また、同じ遺伝子を用いて129系統由来のES細胞(E14.1)を用いて遺伝子改変マウスを作出し、短期間でのバッククロスの方法(体外受精)により従来の方法の約1/3の期間で遺伝的背景を変える事に成功した。また、現在C57BL/6系統由来ES細胞について我々が樹立したST/b細胞とブルース4細胞とで遺伝子改変マウスを作出し、その性状を検討しているところである。

研究成果
(51件)

すべてその他

すべて文献書誌 (51件)

[文献書誌] Voronov, E.: "Interleukin 1 is required for tumor invasiveness and angiogenesis"Proc.Natl.Acad.Sci. USA. (in press). (2003)
[文献書誌] Nakae, S.: "Interleukin-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response"Int.Immunol.. (in press). (2003)
[文献書誌] Ohtaki, H.: "Suppression of oxidative neuronal damage after transient middle cerebral artery occlusion in mice lacking interleukin-1"Neuroscience Res.. (in press). (2003)
[文献書誌] Sashinami, H.: "Effective induction of acquired resistance to Listeria monocytogenes by immunizing mice with in vivo-infected dendritic cells"Infect.Immun.. 71. 117-125 (2003)
[文献書誌] Li, H.: "Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2. Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2"Eur.J.Neurosci.. (in press). (2003)
[文献書誌] Tanaka, J.: "Latent HIV-1 reactivation in transgenic mice requires cell cycle-dependent demethylation of CREB/ATF sites in the LTR"AIDS. 17. 167-175 (2003)
[文献書誌] Iwakura, Y.: "Autoimmune chronic inflammatory arthropathy in mice transgenic for the HTLV-1 tax gene"Gann Monograph. (in press). (2003)
[文献書誌] Nakae, S.: "IL-1-induced TNFα elicits inflammatory cell infiltration in the skin by inducing interferon-γ-inducible protein-10 in the elicitation phase of contact hypersensitivity response"Int.Immunol.. 15. 251-260 (2003)
[文献書誌] Ikegaya, Y.: "Interleukin-1β abrogates long-term depression of hippocampal CA1 synaptic transmission"Synapse. 47. 54-57 (2003)
[文献書誌] Kurisaki, T.: "Phenotypic analysis of Meltrin α (ADAM12)-deficient mice : involvement of Meltrin a in adipogenesis and myogenesis"Mol.Cell.Biol.. 23. 55-61 (2003)
[文献書誌] Yokoyama, H.: "Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene"J.Gen.Virol.. 83. 141-150 (2002)
[文献書誌] Yano, A.: "Roles of IFN-γ on stage conversion of an obligate intracellular protozoan parasite, Toxoplasma gondii"Int.Rev.Immunol.. 21. 405-421 (2002)
[文献書誌] Desaki, M.: "Role of interferon-γ in the development of murine bronchus-associated lymphoid tissues induced by silica in vivo"Toxicol.Appl.Pharmacol.. 185. 1-7 (2002)
[文献書誌] Yoshida, M.: "Differential localization of colitogenic Th1 and Th2 cells monospecific to a microflora-associated antigen in mice"Gastroenterology. 123. 1949-1961 (2002)
[文献書誌] Oguri, S.: "Primary role of interleukin-1α and Interleukin-1β in lipopolysaccharide-induced hypoglycemia in mice"Clin.Diagn.Lab.Immunol.. 9. 1307-1312 (2002)
[文献書誌] Kakuta, S.: "Genomic structure of the mouse 2',5'-oligoadenylate synthetase gene family"J.Interferon Cytokine Res.. 22. 981-993 (2002)
[文献書誌] Sakamaki, K.: "Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart"Cell Death and Differentiation. 11. 1196-1206 (2002)
[文献書誌] Nakae, S.: "Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, resulting in the suppression of allergic cellular and humoral responses"Immunity. 17. 375-387 (2002)
[文献書誌] Yan, X.: "Antibacterial effect of Kampo herbal formulation Hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang) on Helicobacter pylori infection in mice"Microbiol.Immunol.. 46. 475-482 (2002)
[文献書誌] Iwakura, Y.: "Roles of IL-1 in the development of rheumatoid arthritis : Consideration from mouse models"Cytokine Growth Factor Rev.. 13. 341-355 (2002)
[文献書誌] Mizuki, M.: "Comparison of host resistance to primary and secondary Listeriamonocytogenes infections in mice by intranasal and intravenous routes"Infect.Immun.. 70. 4805-4811 (2002)
[文献書誌] Shiraishi, K.: "Roles of RecJ, RecO, and RecR in RecET-mediated illegitimate recombination in Escherichia coli"J.Bacteriol.. 184. 4715-4721 (2002)
[文献書誌] Minami, M.: "Role of IFN-γ and tumor necrosis factor-α in herpes simplex virus type infection"J.Interferon Cytokine Res.. 22. 671-676 (2002)
[文献書誌] Ishida, Y.: "A pivotal involvement of IFN-γ in the pathogenesis of acetaminophen-induced acute liver injury"FASEB J.. 16. 1227-1236 (2002)
[文献書誌] Konishi, H.: "IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions"Proc.Natl.Acad.Sci. USA. 99. 11340-11345 (2002)
[文献書誌] Sasaki, S.: "Roles of gamma interferon and tumor necrosis factor-alpha in shiga toxin lethality"Microb.Pathog.. 33. 43-47 (2002)
[文献書誌] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"Nat.Immunol.. 3. 667-672 (2002)
[文献書誌] Yamamoto, S.: "Mice deficient in nervous system-specific carbohydrate epitope HNK-1 exhibit impaired synaptic plasticity and spatial learning"J.Biol.Chem.. 277. 27227-27231 (2002)
[文献書誌] Mizushima, H.: "Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1"J.comparative Neurol.. 448. 203-216 (2002)
[文献書誌] Asada, H.: "Significant antitumor effects obtained by autologous tumor cell vaccine engineered to secrete interleukin (IL)-12 and IL-18 by means of the EBV/lipoplex"Molec.Therapy. 5. 609-616 (2002)
[文献書誌] Oguro, T.: "Involvement of tumor necrosis factorα rather than interleukin-1 or nitric oxides in the HEME Oxygenase-1 gene expression by lipopolysaccharide in the mouse liver"FEBS Letters. 516. 63-66 (2002)
[文献書誌] Battsetseg, B.: "Immune responses of interferon γ (IFN-γ) knock out mice to repeated Haemaphysalis longicornis (Acari : Ixodidae) nymph infestations"J.Med.Entomol.. 39. 173-176 (2002)
[文献書誌] Asahi, Y.: "Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines"J.Immunol.. 168. 2930-2938 (2002)
[文献書誌] Furuzawa, M.: "Diurnal variation of heart rate, locomotor activity, and body temperature in interleukin-1 α/β doubly deficient mice"Exp.Anim.. 51. 49-56 (2002)
[文献書誌] Shinozawa, Y.: "Role of interferon-gamma in inflammatory responses in murine respiratory infection with Legionella pneumophila"J.Med.Microbiol.. 51. 225-230 (2002)
[文献書誌] Kyuwa, S.: "Acute hepatic failure in IFN-γ-deficient BALB/c mice after murine coronavirus infection"Virus Research. 83. 169-177 (2002)
[文献書誌] Nagai, Y.: "Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide"Blood. 99. 1699-1705 (2002)
[文献書誌] Brough, D.: "Purinergic (P2X7) receptor activation of microglia induces cell death via an interleukin-1-independent mechanism"Mol.Cell.Neurosci.. 19. 272-280 (2002)
[文献書誌] Kakuta, S.: "Inhibition of B16 melanoma experimental metastasis by interferon-γ through direct inhibition of cell proliferation and activation of antitumour host mechanisms"Immunology. 105. 92-100 (2002)
[文献書誌] Saijo, S.: "Suppression of autoimmune arthritis in IL-1-deficient mice in which T cell activation is impaired due to low levels of CD40L and OX40 expression on T cells"Arth.Rheum.. 46. 533-544 (2002)
[文献書誌] Le Feuvre, R.A.: "Priming of macrophages with LPS potentiates P2X7 mediated cell death via a caspase-1 dependent mechanism, independently of cytokine production"J.Biol.Chem.. 277. 3210-3218 (2002)
[文献書誌] 岩倉洋一郎: "関節リウマチモデルマウス"医学のあゆみ. (印刷中). (2003)
[文献書誌] 岩倉洋一郎: "関節リウマチモデルマウスと創薬への応用"日本薬理学雑誌. 120. 303-313 (2002)
[文献書誌] 中江進: "接触型過敏症に於けるサイトカインの役割"臨床免疫. 38. 171-178 (2002)
[文献書誌] 岩倉洋一郎: "IL-1の過剰シグナルによる自己免疫の誘導"蛋白質・核酸・酵素. 47(増刊). 2349-2354 (2002)
[文献書誌] 岩倉洋一郎: "関節炎発症に於けるIL-1の役割"最新医学. 57. 840-818 (2002)
[文献書誌] 岩倉洋一郎: "ヒトレトロウイルス感染症モデル:エイズおよび関節リウマチモデル"病理と臨床. 20. 291-299 (2002)
[文献書誌] 宝来玲子: "IL-1Raノックアウトマウスの関節炎"炎症と免疫. 10. 85-89 (2002)
[文献書誌] 岩倉洋一郎: "動物発生工学"朝倉書店. 254 (2002)
[文献書誌] 浅島誠: "バイオサイエンスの新世紀 15「生命工学・新しい生命へのアプローチ」"共立出版社. 291 (2002)
[文献書誌] 井上達: "ヒト型モデル動物"シュプリンガー・フェアラーク東京. 221 (2002)

2002 年度 実績報告書

各種近交系由来ES細胞の樹立

研究代表者

須藤 カツ子 東京大学, 医科学研究所, 助手 (50126091)

研究成果

[文献書誌] Voronov, E.: "Interleukin 1 is required for tumor invasiveness and angiogenesis"Proc.Natl.Acad.Sci. USA. (in press). (2003)

[文献書誌] Nakae, S.: "Interleukin-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response"Int.Immunol.. (in press). (2003)

[文献書誌] Ohtaki, H.: "Suppression of oxidative neuronal damage after transient middle cerebral artery occlusion in mice lacking interleukin-1"Neuroscience Res.. (in press). (2003)

[文献書誌] Sashinami, H.: "Effective induction of acquired resistance to Listeria monocytogenes by immunizing mice with in vivo-infected dendritic cells"Infect.Immun.. 71. 117-125 (2003)

[文献書誌] Li, H.: "Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2. Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2"Eur.J.Neurosci.. (in press). (2003)

[文献書誌] Tanaka, J.: "Latent HIV-1 reactivation in transgenic mice requires cell cycle-dependent demethylation of CREB/ATF sites in the LTR"AIDS. 17. 167-175 (2003)

[文献書誌] Iwakura, Y.: "Autoimmune chronic inflammatory arthropathy in mice transgenic for the HTLV-1 tax gene"Gann Monograph. (in press). (2003)

[文献書誌] Nakae, S.: "IL-1-induced TNFα elicits inflammatory cell infiltration in the skin by inducing interferon-γ-inducible protein-10 in the elicitation phase of contact hypersensitivity response"Int.Immunol.. 15. 251-260 (2003)

[文献書誌] Ikegaya, Y.: "Interleukin-1β abrogates long-term depression of hippocampal CA1 synaptic transmission"Synapse. 47. 54-57 (2003)

[文献書誌] Kurisaki, T.: "Phenotypic analysis of Meltrin α (ADAM12)-deficient mice : involvement of Meltrin a in adipogenesis and myogenesis"Mol.Cell.Biol.. 23. 55-61 (2003)

[文献書誌] Yokoyama, H.: "Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene"J.Gen.Virol.. 83. 141-150 (2002)

[文献書誌] Yano, A.: "Roles of IFN-γ on stage conversion of an obligate intracellular protozoan parasite, Toxoplasma gondii"Int.Rev.Immunol.. 21. 405-421 (2002)

[文献書誌] Desaki, M.: "Role of interferon-γ in the development of murine bronchus-associated lymphoid tissues induced by silica in vivo"Toxicol.Appl.Pharmacol.. 185. 1-7 (2002)

[文献書誌] Yoshida, M.: "Differential localization of colitogenic Th1 and Th2 cells monospecific to a microflora-associated antigen in mice"Gastroenterology. 123. 1949-1961 (2002)

[文献書誌] Oguri, S.: "Primary role of interleukin-1α and Interleukin-1β in lipopolysaccharide-induced hypoglycemia in mice"Clin.Diagn.Lab.Immunol.. 9. 1307-1312 (2002)

[文献書誌] Kakuta, S.: "Genomic structure of the mouse 2',5'-oligoadenylate synthetase gene family"J.Interferon Cytokine Res.. 22. 981-993 (2002)

[文献書誌] Sakamaki, K.: "Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart"Cell Death and Differentiation. 11. 1196-1206 (2002)

[文献書誌] Nakae, S.: "Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, resulting in the suppression of allergic cellular and humoral responses"Immunity. 17. 375-387 (2002)

[文献書誌] Yan, X.: "Antibacterial effect of Kampo herbal formulation Hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang) on Helicobacter pylori infection in mice"Microbiol.Immunol.. 46. 475-482 (2002)

[文献書誌] Iwakura, Y.: "Roles of IL-1 in the development of rheumatoid arthritis : Consideration from mouse models"Cytokine Growth Factor Rev.. 13. 341-355 (2002)

[文献書誌] Mizuki, M.: "Comparison of host resistance to primary and secondary Listeriamonocytogenes infections in mice by intranasal and intravenous routes"Infect.Immun.. 70. 4805-4811 (2002)

[文献書誌] Shiraishi, K.: "Roles of RecJ, RecO, and RecR in RecET-mediated illegitimate recombination in Escherichia coli"J.Bacteriol.. 184. 4715-4721 (2002)

[文献書誌] Minami, M.: "Role of IFN-γ and tumor necrosis factor-α in herpes simplex virus type infection"J.Interferon Cytokine Res.. 22. 671-676 (2002)

[文献書誌] Ishida, Y.: "A pivotal involvement of IFN-γ in the pathogenesis of acetaminophen-induced acute liver injury"FASEB J.. 16. 1227-1236 (2002)

[文献書誌] Konishi, H.: "IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions"Proc.Natl.Acad.Sci. USA. 99. 11340-11345 (2002)

[文献書誌] Sasaki, S.: "Roles of gamma interferon and tumor necrosis factor-alpha in shiga toxin lethality"Microb.Pathog.. 33. 43-47 (2002)

[文献書誌] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"Nat.Immunol.. 3. 667-672 (2002)

[文献書誌] Yamamoto, S.: "Mice deficient in nervous system-specific carbohydrate epitope HNK-1 exhibit impaired synaptic plasticity and spatial learning"J.Biol.Chem.. 277. 27227-27231 (2002)

[文献書誌] Mizushima, H.: "Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1"J.comparative Neurol.. 448. 203-216 (2002)

[文献書誌] Asada, H.: "Significant antitumor effects obtained by autologous tumor cell vaccine engineered to secrete interleukin (IL)-12 and IL-18 by means of the EBV/lipoplex"Molec.Therapy. 5. 609-616 (2002)

[文献書誌] Oguro, T.: "Involvement of tumor necrosis factorα rather than interleukin-1 or nitric oxides in the HEME Oxygenase-1 gene expression by lipopolysaccharide in the mouse liver"FEBS Letters. 516. 63-66 (2002)

[文献書誌] Battsetseg, B.: "Immune responses of interferon γ (IFN-γ) knock out mice to repeated Haemaphysalis longicornis (Acari : Ixodidae) nymph infestations"J.Med.Entomol.. 39. 173-176 (2002)

[文献書誌] Asahi, Y.: "Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines"J.Immunol.. 168. 2930-2938 (2002)

[文献書誌] Furuzawa, M.: "Diurnal variation of heart rate, locomotor activity, and body temperature in interleukin-1 α/β doubly deficient mice"Exp.Anim.. 51. 49-56 (2002)

[文献書誌] Shinozawa, Y.: "Role of interferon-gamma in inflammatory responses in murine respiratory infection with Legionella pneumophila"J.Med.Microbiol.. 51. 225-230 (2002)

[文献書誌] Kyuwa, S.: "Acute hepatic failure in IFN-γ-deficient BALB/c mice after murine coronavirus infection"Virus Research. 83. 169-177 (2002)

[文献書誌] Nagai, Y.: "Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide"Blood. 99. 1699-1705 (2002)

[文献書誌] Brough, D.: "Purinergic (P2X7) receptor activation of microglia induces cell death via an interleukin-1-independent mechanism"Mol.Cell.Neurosci.. 19. 272-280 (2002)

[文献書誌] Kakuta, S.: "Inhibition of B16 melanoma experimental metastasis by interferon-γ through direct inhibition of cell proliferation and activation of antitumour host mechanisms"Immunology. 105. 92-100 (2002)

[文献書誌] Saijo, S.: "Suppression of autoimmune arthritis in IL-1-deficient mice in which T cell activation is impaired due to low levels of CD40L and OX40 expression on T cells"Arth.Rheum.. 46. 533-544 (2002)

[文献書誌] Le Feuvre, R.A.: "Priming of macrophages with LPS potentiates P2X7 mediated cell death via a caspase-1 dependent mechanism, independently of cytokine production"J.Biol.Chem.. 277. 3210-3218 (2002)

[文献書誌] 岩倉洋一郎: "関節リウマチモデルマウス"医学のあゆみ. (印刷中). (2003)

[文献書誌] 岩倉洋一郎: "関節リウマチモデルマウスと創薬への応用"日本薬理学雑誌. 120. 303-313 (2002)

[文献書誌] 中江進: "接触型過敏症に於けるサイトカインの役割"臨床免疫. 38. 171-178 (2002)

[文献書誌] 岩倉洋一郎: "IL-1の過剰シグナルによる自己免疫の誘導"蛋白質・核酸・酵素. 47(増刊). 2349-2354 (2002)

[文献書誌] 岩倉洋一郎: "関節炎発症に於けるIL-1の役割"最新医学. 57. 840-818 (2002)

[文献書誌] 岩倉洋一郎: "ヒトレトロウイルス感染症モデル:エイズおよび関節リウマチモデル"病理と臨床. 20. 291-299 (2002)

[文献書誌] 宝来玲子: "IL-1Raノックアウトマウスの関節炎"炎症と免疫. 10. 85-89 (2002)

[文献書誌] 岩倉洋一郎: "動物発生工学"朝倉書店. 254 (2002)

[文献書誌] 浅島誠: "バイオサイエンスの新世紀 15「生命工学・新しい生命へのアプローチ」"共立出版社. 291 (2002)

[文献書誌] 井上達: "ヒト型モデル動物"シュプリンガー・フェアラーク東京. 221 (2002)

2002 年度実績報告書

須藤カツ子東京大学, 医科学研究所, 助手 (50126091)