Trial of human tissue-substituted mice and its application to human diseases.

2008 Fiscal Year Final Research Report

• Project/Area Number: 18200028
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: YONEKAWA Hiromichi Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 参事研究員 (30142110)
• Co-Investigator(Kenkyū-buntansha): KOHARA Michinori 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 参事研究員 (10250218)
• Co-Investigator(Renkei-kenkyūsha): TAYA Choji 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 主任研究員 (90175456) ; SHITARA Hiroshi 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (90321885) ; ISHII Rie 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (00425688) ; SHUDA Masahiro 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (10356256)
• Project Period (FY): 2006 – 2008
• Keywords: 標的細胞ノックアウト法 / TRECK法 / SCIDマウス / ヒト細胞置換マウス / 肝実質細胞

Research Abstract

体内にヒトの肝臓を持つことのできる遺伝子改変マウスの作製を行った。ヒト細胞を移植できるSCIDマウスに標的細胞ノックアウト法を施し、マウス肝細胞を部分的に除去した後、ヒトの培養肝細胞を移植した。その結果、ヒトの肝臓がマウスの肝臓内で生着し、血液中にヒトのアルブミンが放出されたことを確認した。しかし、高い頻度でのヒト肝細胞への置換には至らす、現在その条件をさらに検討している。

Research Products

• [Journal Article] Disruption of IFN Signaling and HCV Synergistically Enhance Lympho- proliferation through Type II CD95 and Interleukins. (2009)
  • Author(s): K. Machida, K. Tsukiyama-Kohara, E. Seike, S. Tone, Y. Hayashi, Y. Kasama, M. Shimizu, H. Takahashi, C. Taya, H. Yonekawa, N. Tanaka, M. Kohara.
  • Journal Title: Gastroenterology in press Pages: 0
• [Journal Article] RNA polymerase to make a highly active JFH1-type polymerase by mutation of the thumb domain. (2009)
  • Author(s): L. Weng, J. Du, J. Zhou, J. Ding, T. Wakita, M. Kohara, T. Toyoda.
  • Journal Title: Arch Virol. 154 Pages: 765-773
• [Journal Article] Synthesis of nuclease-resistant siRNAs possessing universal overhangs. (2009)
  • Author(s): Y. Ueno, Y. Watanabe, A. Shibata, K. Yoshikawa, T. Takano, M. Kohara, Y Kitade
  • Journal Title: Bioorganic & Medicinal Chemistry. 17 Pages: 1974-81
  • Peer Reviewed
• [Journal Article] A mutational shift from domain III to II in the internal ribosome entry site of hepatitis C virus after interferon-ribavirin therapy. (2008)
  • Author(s): K. Ogata, T. Kashiwagi, J. Iwahashi, K. Hara, H. Honda, T. Ide, R. Kumashiro, M. Kohara, M Sata, N. Hamada.
  • Journal Title: Arch Virol. 153(8) Pages: 1575-9
  • Peer Reviewed
• [Journal Article] Prior immunization with SARS- CoV nucleocapsid protein causes severe pneumonia in mice infected with SARS- CoV. (2008)
  • Author(s): F. Yasui, C. Kai, M. Kitabatake, S. Inoue, M. Yoneda, S. Yokochi, R. Kase, S. Sekiguchi, K Morita, T Hishima, H Suzuki, K. Karamatsu, Y. Yasutomi, H. Shida, M. Kidokoro, K. Mizuno, K. Matsushima, M. Kohara.
  • Journal Title: J. Immunology 181 Pages: 6337-48
  • Peer Reviewed
• [Journal Article] Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus express- ing short hairpin RNA. (2008)
  • Author(s): N. Sakamoto, Y. Tanabe, T. Yokota, K. Satoh, Y. Sekine-Osajima, M. Nakagawa, Y. Itsui, M. Tasaka, Y. Sakurai, C.-H. Chen, M. Yano, S. Ohkoshi, Y. Aoyagi, S. Maekawa, N. Enomoto, M. Kohara, M. Watanabe.
  • Journal Title: J. Gastroentero- logy Hepatology. 23 Pages: 1437-47
  • Peer Reviewed
• [Journal Article] Comparative aspects on the role of polypyrimidine tract-binding protein in internal initiation of hepatitis C virus and picornavirus RNAs (2008)
  • Author(s): T. Nishimura, M. Saito, T. Takano, A. Nomoto, M. Kohara, K. Tsukiyama Kohara.
  • Journal Title: Compara. Immu. Microbio. Infect. Dises. 31 Pages: 435-448
  • Peer Reviewed
• [Journal Article] Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein-tyrosine kinase Syk. (2008)
  • Author(s): S. Inubushi, M. Nagano-Fujii, K. Kitayama, M. Tanaka, A. Chunying, H. Yokozaki, H. Yamamura, H. Nuriya, M. Kohara, K. Sada, H. Hotta.
  • Journal Title: J. Gen. Virology 89 Pages: 1231-1242
  • Peer Reviewed
• [Journal Article] Therapeutic application of RNA interference for Hepatitis C Virus. (2007)
  • Author(s): T. Watanabe, T. Umehara, M. Kohara.
  • Journal Title: Advanced Drug Delivery Reviews 59 Pages: 1263-1276
  • Peer Reviewed
• [Journal Article] Liver target delivery of small interfering RNA to the HCV gene by lactosylated cationic liposome. (2007)
  • Author(s): T. Watanabe, T. Umehara, F. Yasui, S. Nakagawa, J. Yano, T. Ohgi, S. Sonoke, K. Inoue, M. Yoshiba, M. Kohara.
  • Journal Title: J. Hepatology 47 Pages: 744-750
  • Peer Reviewed
• [Journal Article] Survival of liver failure pigs by transplantation of reversibly immortalized human hepatocytes with Tamoxifen-mediated self-recombination. (2007)
  • Author(s): T. Totsugawa, C. Yong, J.D. Rivas-Carrillo, A. Soto-Gutierrez, N. Navarro-Alvarez, H. Noguchi, T. Okitsu, K.A. Westerman, M. Kohara, M. Reth, N. Tanaka, P. Leboulch, N. Kobayashi.
  • Journal Title: J. Hepatology 47 Pages: 74-82
  • Peer Reviewed
• [Journal Article] Identification of CTL epitopes in hepatitis C virus by a genome-w ide computational scanning and a rational design of peptide vaccine. (2007)
  • Author(s): T. Mashiba, K. Udaka, Y. Hirachi, Y. Hiasa, T. Miyakawa, Y. Satta, T. Osoda, S. Kataoka, M. Kohara, M. Onji.
  • Journal Title: Immunogenetics 59 Pages: 197-209
  • Peer Reviewed
• [Journal Article] Evaluation of a Cyclophilin Inhibitor in Hepatitis C Virus-Infected Chimeric Mice In Vivo. (2007)
  • Author(s): K. Inoue, T. Umehara, U. T. Ruegg, F. Yasui, T. Watanabe, H. Yasuda, M. Yoshiba, J.-M. Dumont, P. Scalfaro, M. Kohara.
  • Journal Title: Hepatology 45 Pages: 921-928
  • Peer Reviewed
• [Journal Article] Inhibition of Hsp90 suppresses HCV replication in replicon cell lines and in chimeric mice with humanized liver. (2007)
  • Author(s): S. Nakagawa, T. Umehara, C. Matsuda, S. Kuge, M. Sudoh M. Kohara.
  • Journal Title: Biochem. Biophys. Res. Commun. 353 Pages: 882-888
  • Peer Reviewed
• [Journal Article] SARS- CoV spike protein recombinant vaccinia virus efficiently induces neutralizing antibodies in spite of pre-immunization with vaccinia virus. (2007)
  • Author(s): M. Kitabatake, S. Inoue, F. Yasui, S. Yokochi, M. Arai, K. Morita, H. Shida, M. Kidokoro, F. Murai, M. L.Quynh, K. Matsushima, M. Kohara.
  • Journal Title: Vaccine 25 Pages: 630-637
  • Peer Reviewed
• [Presentation] 標的細胞ノックアウト法の胎仔組織への応用 (2008)
  • Author(s): 松岡邦枝、土屋真衣子、設楽浩志、松尾千古、河野憲二、米川博通
  • Organizer: BMB2008(第31回日本分子生物学会年会、第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 20081209-12
• [Presentation] Improvement of a tissue-specific gene expression for TRECK method using a BAC clone. (2008)
  • Author(s): Yonekawa, H., Shibata, K., Sekine, M., Matsuoka, K., Shitara, H., Taya, C. Amano, T.
  • Organizer: The 22nd International Mammalian Genome Conference (IMGC2008)
  • Place of Presentation: Prague, Czech
  • Year and Date: 20081102-05
• [Presentation] 新規HCV持続感染モデルマウスの作製とその病態解析 (2008)
  • Author(s): 関口 敏、飛田良美、千代智子、小原道法
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 20081026-28
• [Presentation] 標的細胞ノックアウト法の胎仔組織への応用 (2008)
  • Author(s): 松岡邦枝、土屋真衣子、設楽浩志、松尾千古、河野憲二、米川博通
  • Organizer: 日本実験動物科学技術2008(第55回日本実験動物学会総会・第42回日本実験動物技術者協会総会
  • Place of Presentation: 仙台
  • Year and Date: 20080515-17
• [Presentation] ヒト肝置換Tgマウスの作製方法 (2008)
  • Author(s): 米川博通、松岡邦枝
  • Organizer: 第7回研究交流フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2008-02-27
• [Presentation] Suppression of serine palmitoyltransferase inhibits HCV replication in mice with chimeric human liver. (2006)
  • Author(s): Umehara T., Sudoh M., Yasui F., Nakagawa S. and Kohara M.
  • Organizer: 20^<th> IUBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto
  • Year and Date: 20060618-23