Analysis of T cell leukemia/lymphoma in a human T-cell leukemia virus type I tax gene transgenic mouse model

• Project/Area Number: 19500363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kumamoto University
• Principal Investigator: OHSUGI Takeo Kumamoto University, 生命資源研究支援センター, 准教授 (00211102)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: HTLV-1 / 成人T細胞白血病 / 関節炎 / tax遺伝子 / ATL / マウス / 遺伝子改変マウス

Research Abstract

ヒトT細胞白血病ウイルスtax遺伝子をT細胞特異的に発現するマウスを作出したところ、T細胞リンパ腫と関節炎を発症した。Tax遺伝子発現およびサイトカイン発現の違いから、両疾患に関与する細胞のフェノタイプは各々異なるものと考えられた。がん抑制遺伝子p53に、多くのがんで観察される変異はみられなかったが、その機能は、疾患発症月齢に到達する以前に有意に低下しており、疾患発症に重要な役割を果たしていることが示唆された。

Research Products

• [Journal Article] The anti-retroviral potency of APOBEC1 deaminase from small animal species (2008)
  • Author(s): Ikeda, T., Ohsugi, T., Kimura, T. Matsushita, S., Maeda, Y., Harada, S., and Koito, A.
  • Journal Title: Nucleic Acids Res 36 Pages: 6859-6871
  • Peer Reviewed
• [Journal Article] Invited review : Current topics in prevention of Human T-cell leukemia virus type I (HTLV-I) infection : NF-KB inhibitors and APOBEC3 (2008)
  • Author(s): Ohsugi, T. and Koito, A.
  • Journal Title: International Reviews of Immunology 27 Pages: 177-205
  • Peer Reviewed
• [Journal Article] Current topics in prevention of Human T-cell leukemia virus type l(HTLV-I)infection : NF-kB inhibitors and APOBEC3 (2008)
  • Author(s): Ohsugi, T.
  • Journal Title: International Reviews of Immunology 27 Pages: 177-205
  • Peer Reviewed
• [Journal Article] The anti-retroviral potency of APOBECl deaminase from small animal species (2008)
  • Author(s): Ikeda, T.
  • Journal Title: Nucleic Acids Research 36 Pages: 6859-6871
  • Peer Reviewed
• [Journal Article] Current topics in prevention of Human T-Cell Leukemia Virus Type I Infection: NF-κB inhitors and APOBEC3 (2008)
  • Author(s): Ohsugi, T.
  • Journal Title: International Reviews of Immunology 27 Pages: 1-29
  • Peer Reviewed
• [Journal Article] Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation in mice inoculated with Tax-deficient adult T-cell leukemia-derived cell lines (2007)
  • Author(s): Ohsugi, T., Kumasaka, T., Okada, S., Ishida, T., Yamaguchi, K., Horie, R., Watanabe, T. and Umezawa, K.
  • Journal Title: Cancer letters 257 Pages: 206-215
  • Peer Reviewed
• [Journal Article] Development T cell leukemia/lymphoma and arthropathy in transgenic mice carrying human T cell leukemia virus type I tax gene (2007)
  • Author(s): Ohsugi, T., Kumasaka, T., Okada, S. andUrano, T.
  • Journal Title: AIDS Res. Hum. Retroviruses 23 Pages: 583-583
• [Journal Article] The Tax protein of HTLV-1 promotes oncogenesis in not only immature T cells but also mature T cells (2007)
  • Author(s): Ohsugi, T., Kumasaka, T., Okada, S. and Urano, T.
  • Journal Title: Nature Medicine 13 Pages: 527-528
  • Peer Reviewed
• [Journal Article] Human T cell leukemia virus type I is resistant to the antiviral effects of APOBEC3 (2007)
  • Author(s): Ohsugi, T. and Koito, A.
  • Journal Title: J. Virol. Methods 139 Pages: 93-96
  • Peer Reviewed
• [Journal Article] Human T cell leukemia virus type I is resistant to the antiviral effects of APOBEC3 (2007)
  • Author(s): Ohsugi, T.
  • Journal Title: J. Virol, Methods 139 Pages: 93-96
  • Peer Reviewed
• [Journal Article] Development T cell leukemia/lymphoma and arthropathy in transgenic mice carrying human T cell leukemia virus type Itax gene (2007)
  • Author(s): Ohsugi, T.
  • Journal Title: AIDS Res. Hum. Retroviruses 23 Pages: 583-583
  • Peer Reviewed
• [Journal Article] Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation in mice inoculated with Tax-deficient adult Tcell leukemia-derived cell lines (2007)
  • Author(s): Ohsugi, T.
  • Journal Title: Cancer letters 257 Pages: 206-215
  • Peer Reviewed
• [Journal Article] Tax protein of HTLV-1 promotes oncogenesis in not only immature T cells but also mature T cells (2007)
  • Author(s): Ohsugi, T.
  • Journal Title: Nature Medicine 13 Pages: 527-528
  • Peer Reviewed
• [Presentation] ヒトT細胞白血病ウイルスI型(HTLV-I)tax遺伝子導入マウスにおけるp53機能の解析 (2008)
  • Author(s): 大杉剛生
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
• [Presentation] ヒトT細胞白血病ウイルスI型(HTLV-I)tax遺伝子導入マウスにみられた成熟T細胞白血病・リンパ腫の解析 (2008)
  • Author(s): 大杉剛生
  • Organizer: 日本実験動物科学技術
  • Place of Presentation: 仙台
• [Presentation] Transgenic Mice Expressing the HTLV-1 Tax Gene Develop Two Distinct Diseases : Leukemia and Arthropathy (2008)
  • Author(s): Takeo Ohsugi
  • Organizer: 99th AACR Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] The Anti-HIV-1 Potency of APOBEC1 Cytidine Deaminase from Small Animal Species (2008)
  • Author(s): Terumasa Ikeda
  • Organizer: The 15th Conference on Retroviruses and Opportunistic Infections
  • Place of Presentation: Boston, USA
• [Presentation] Transgenic Mice Expressing the HTLV-l Tax Gene Develop Two Distinct Diseases : Leukemia and Arthropathy (2008)
  • Author(s): Takeo Ohsugi
  • Organizer: 99th AACR Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] ヒトT細胞白血病ウイルスl型(HTLV-l)tax遺伝子導入マウスにみられた成熟T細胞白血病・リンパ腫の解析 (2008)
  • Author(s): 大杉剛生
  • Organizer: 日本実験動物科学技術2008
  • Place of Presentation: 仙台
• [Presentation] ヒトT細胞白血病ウイルスl型(HTLV-l)tax遺伝子導入マウスにおけるp53機能の解析 (2008)
  • Author(s): 大杉 剛生
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
• [Presentation] Leading Project for Personalized Medicine at the Center for Clinical Pharmaceutical Sciences (CCPS) (2008)
  • Author(s): Irie T.
  • Organizer: The 6th Kumamoto University Forum in Surabaya
  • Place of Presentation: Surabaya Indonesia
• [Presentation] The Anti-HIV-1 Potency of APOSEC1 Cytidine Deaminase from Small Animal Species (2008)
  • Author(s): Ikeda, T.
  • Organizer: The 15th Conference on Retroviruses and Opportunistic Infections
  • Place of Presentation: Boston,USA
• [Presentation] マウスからの蟯虫駆除とその後の経過について (2007)
  • Author(s): 吉住正等美
  • Organizer: 第41回日本実験動物技術者協会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-07-06
• [Presentation] 哺乳類APOBEC1によるHIV制御機構の解析 (2007)
  • Author(s): 池田輝政
  • Organizer: The anti-HIV potency of APOBEC1 cytidine deaminase from mammalian species第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ヒトT細胞白血病ウイルスI型(HTLV-I)Tax遺伝子導入マウスの病態解析 (2007)
  • Author(s): 大杉剛生
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] 哺乳類APOBEC1分子によるHIV複製の阻害 (2007)
  • Author(s): 池田輝政
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Development T cell leukemia/lymphoma and arthropathy in transgenic mice carrying human T cell leukemia virus type I tax gene (2007)
  • Author(s): Takeo Ohsugi
  • Organizer: 13th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Hakone, Japan
• [Presentation] X線生体撮像システムを用いたマウス関節炎の解析 (2007)
  • Author(s): 坂本哲志
  • Organizer: 第30回日本実験動物技術者協会九州支部総会第26回日本実験動物技術者協会九州支部研究発表会
  • Place of Presentation: 鹿児島
• [Presentation] Development T cell leukemia/lymphoma and arthropathy in transgenic mice carrying human T cell leukemia virus type Itax gene (2007)
  • Author(s): Ohsugi, T.
  • Organizer: 13th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Hakone,Japan
• [Presentation] 哺乳類 APOBEC1 分子による HIV 複製の阻害 (2007)
  • Author(s): 池田 輝政
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] 哺乳類 APOBEC1 による HIV 制御機構の解析 (2007)
  • Author(s): 池田 輝政
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Book] ATL、HTLV-1の動物モデル。『HTLV-1と疾患』(渡邊俊樹、上平憲、山口一成編) (2007)
  • Author(s): 大杉剛生
  • Publisher: 文光堂
• [Book] ヒトT細胞白血病ウイルスI型HTLV-Iと疾患 (2007)
  • Author(s): 大杉 剛生
  • Total Pages: 263
  • Publisher: 文光堂
• [Book] Human T-cell Leukemia Virus Type 1 (HTLV-1) and Antiviral Enzyme APOBEC3. ViralGenomes : Diversity, Properties and Parameters, Zhi Feng and Ming Long (eds)
  • Author(s): Ohsugi, T. and Koito, A.
  • Publisher: NOVA Scientific publishers(in press)
• [Book] Viral Genomes ; Human T-cell Leukemia Virus Type l(HTLV-l)and Antiviral Enzyme AP0BEC3
  • Author(s): Ohsugi, T.
  • Publisher: NOVA Scientific publishers(in press)
• [Remarks] Irie T, Hirata S, Maruyama T, Saito H, Kitamura K, Nishikawa T, Hokimoto S, Katsuki H, Morioka H, Ohsugi T, Ikeda T, Ishizuka T, Nakagawa K. Leading Project for Personalized Medicine at the Center for Clinical Pharmaceutical Sciences (CCPS). The 6th Kumamoto University Forum in Surabaya, Nov. 5-6, 2008, Surabaya Indonesia
• [Remarks] Takeo Ohsugi : Tax transgenic mice provide new clues about Human T-cell leukemia virus type 1 (HTLV-1) disorder (invited speaker). "Advancel Diagnosis and Therapy of Refractory Diseases Caused by Viral Infection" Kagoshima University International Symposium, 3. 27, 2008, Kagoshima, Japan