Generation of a mouse model that shows specific features of human diseases.

2011 Fiscal Year Final Research Report

• Project/Area Number: 22659147
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Hiroshima University
• Principal Investigator: CHAYAMA Kazuaki 広島大学, 大学院・医歯薬学総合研究科, 教授 (00211376)
• Project Period (FY): 2010 – 2011
• Keywords: 肝臓学

Research Abstract

Small animal model such as knockout mouse is a valuable tool to study human diseases. We infected human hepatocyte chimeric mice with hepatitis B virus and administered human peripheral white blood cells. The mice developed fulminant hepatitis like massive human liver cell necrosis. The mouse hepatocyte death has been found to be mediated with FAS-FASL system via NK cell response mediated by dendritic cells. This model will be useful to develop treatment against fulminant hepatitis B.

Research Products

• [Journal Article] Severe necroinflammatory reactio ncaused by natural killer by Fas/ FasL interaction and dendritic cells in human hepatocyte chimeric mouse (2012)
  • Author(s): Okazaki A, Hiraga N, Imamura M, NelsonHayes C, Tsuge M, Takahashi S, Aikata H, Abe H, Miki D, Ochi H, Tateno C, Yoshizato K, Ohdan H, Chayama K.
  • Journal Title: Hepatology 2012. Volume: in press Pages: 25651
  • DOI: doi:10.1002/hep.25651
  • Peer Reviewed
• [Journal Article] Toward the establishment of a prediction system for the personalized treatment of chronic hepatitis C (2012)
  • Author(s): Ochi H, Hayes CN, Abe H, Hayashida Y, Uchiyama T, Kamatani N, Nakamura Y, Chayama K.
  • Journal Title: J Infect Dis Volume: 205 Pages: 204-210
  • DOI: doi:10.1093/infdis/jir726
  • Peer Reviewed
• [Journal Article] Telaprevir with peginterferon and ribavirin for treatment-naive patients chronically infected with HCV of genotype 1 inJapa (2012)
  • Author(s): Kumada H, Toyota J, Okanoue T, Chayama K, Tsubouchi H, Hayashi N.
  • Journal Title: J Hepatol Volume: 56 Pages: 78-84
  • DOI: doi:10.1016/j.jhep.2011.07.016.
  • Peer Reviewed
• [Journal Article] Dual therapy with the nonstructuralprote in 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease in hibitor, asunaprevir, (2012)
  • Author(s): Chayama K, Takahashi S, Toyota J, Karino Y, Ikeda K, Ishikawa H, Watanabe H, McPhee F, Hughes E, KumadaH.
  • Journal Title: in hepatitis C virus genotype 1b-infected null responders Volume: 55 Pages: 742-748
  • DOI: doi:10.1002/hep.24724
  • Peer Reviewed
• [Journal Article] Will there be an HCV meetingin 2020? (2011)
  • Author(s): Wakita T, Suzuki T, Evans MJ, Shimotohno K, Chayama K, Matsuura Y, Hijikata M, Moriishi K, Seya T, Enomoto N, Koike K, Kato N, Kanto T, Hotta H.
  • Journal Title: Summary of the 17thinternational meeting on hepatitis Cvirus and related viruses Volume: 141 Pages: 1-5
  • DOI: doi:10.1053/j.gastro.2011.05.027.
  • Peer Reviewed
• [Journal Article] Effects of hepatitis B virus infection on the interferonresponse in immunodeficient human hepatocyte chimeric mice (2011)
  • Author(s): Tsuge M, Takahashi S, Hiraga N, Fujimoto Y, Zhang Y, Mitsui F, Abe H, Kawaoka T, Imamura M, Ochi H, Hayes CN, Chayama K
  • Journal Title: J Infect Dis 2011 Volume: 204 Pages: 224-228
  • DOI: doi:10.1093/infdis/jir247.
  • Peer Reviewed
• [Journal Article] Hepatitis C virus infection suppresses the interferon response in the liver of the human hepatocyte chimeric mouse (2011)
  • Author(s): Tsuge M, Fujimoto Y, Hiraga N, Zhang Y, Ohnishi M, Kohno T, Abe H, Miki D, Imamura M, Takahashi S, Ochi H, Hayes CN, Miya F, Tsunoda T, Chayama K
  • Journal Title: PLoS One2011 Volume: 6 Pages: 23856
  • DOI: doi:10.1371/journal.pone.0023856.
  • Peer Reviewed
• [Journal Article] Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon (2011)
  • Author(s): Suzuki F, Suzuki Y, Akuta N, Sezaki H, Hirakawa M, Kawamura Y, Hosaka T, Kobayashi M, Saito S, Arase Y, Ikeda K, Kobayashi M, Chayama K, Kamatani N, Nakamura Y, Miyakawa Y, Kumada H
  • Journal Title: ribavirin, and telaprevir. Hepatology 2011 Volume: 53 Pages: 415-421
  • DOI: doi:10.1002/hep.24058.
  • Peer Reviewed
• [Journal Article] In vivo adaptation of hepatitis C virus in chimpanzees for efficient virus production and evasion of apoptosis (2011)
  • Author(s): Saeed M, Shiina M, Date T, Akazawa D, Watanabe N, Murayama A, Suzuki T, Watanabe H, Hiraga N, Imamura M, Chayama K, Choi Y, Krawczynski K, Liang TJ, Wakita T, Kato T
  • Journal Title: Hepatology 2011 Volume: 54 Pages: 425-433
  • DOI: doi:10.1002/hep.24399.
  • Peer Reviewed
• [Journal Article] Impact of radiation and hepatitis virus infection on risk ofhepatocellular carcinoma (2011)
  • Author(s): Ohishi W, Fujiwara S, Cologne JB, Suzuki G, Akahoshi M, Nishi N, Tsuge M, Chayama K.
  • Journal Title: Hepatology 2011 Volume: 53 Pages: 1237-1245
  • DOI: doi:10.1002/hep.24207.
  • Peer Reviewed
• [Journal Article] Elimination of hepatitis Cvirus by short term NS3-4A and NS5B inhibitor combination therapy in human hepatocyte chimeric mice (2011)
  • Author(s): Ohara E, Hiraga N, Imamura M, Iwao E, Kamiya N, Yamada I, Kono T, Onishi M, Hirata D, Mitsui F, Kawaoka T, Tsuge M, Takahashi S, Abe H, Hayes CN, OchiH, Tateno C, Yoshizato K, Tanaka S, Chayama K
  • Journal Title: J Hepatol 2011 Volume: 54 Pages: 872-878
  • DOI: doi:10.1016/j.jhep.2010.08.033.
  • Peer Reviewed
• [Journal Article] IL-28B predictsresponse to chronic hepatitis Ctherapy-fine-mapping and replication study in Asian populations (2011)
  • Author(s): Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Imamura M, Hiraga N, Kawakami Y, Aimitsu S, Kao JH, Kubo M, Tsunoda T, Kumada H, Nakamura Y, Hayes CN, Chayama K
  • Journal Title: J Gen Virol 2011 Volume: 92 Pages: 1071-1081
  • DOI: doi:10.1099/vir.0.029124-0.
  • Peer Reviewed
• [Journal Article] Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers (2011)
  • Author(s): Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, Ikeda K, Kumada H, Toyota J, Morizono T, Tsunoda T, Kubo M, Nakamura Y, Kamatani N, Chayama K
  • Journal Title: Nat Genet 2011 Volume: 43 Pages: 797-800
  • DOI: doi:10.1038/ng.876.
  • Peer Reviewed
• [Journal Article] A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population (2011)
  • Author(s): Mbarek H, Ochi H, Urabe Y, Kumar V, Kubo M, Hosono N, Takahashi A, Kamatani Y, Miki D, Abe H, Tsunoda T, Kamatani N, Chayama K, Nakamura Y, Matsuda
  • Journal Title: Hum Mol Genet 2011 Volume: 20 Pages: 3884-3892
  • DOI: doi:10.1093/hmg/ddr301.
  • Peer Reviewed
• [Journal Article] Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b (2011)
  • Author(s): Kawaoka T, Hayes CN, Ohishi W, Ochi H, Maekawa T, Abe H, Tsuge M, Mitsui F, Hiraga N, Imamura M, Takahashi S, KuboM, Tsunoda T, Nakamura Y, Kumada H, Chayama K.
  • Journal Title: J Hepatol 2011 Volume: 54 Pages: 408-414
  • DOI: doi:10.1016/j.jhep.2010.07.032.
  • Peer Reviewed
• [Journal Article] Rapid emergence of telaprevir resistant hepatitis C virus strain from wildtype clone in vivo (2011)
  • Author(s): Hiraga N, Imamura M, Abe H, Hayes CN, Kono T, Onishi M, Tsuge M, Takahashi S, Ochi H, Iwao E, Kamiya N, Yamada I, Tateno C, Yoshizato K, Matsui H, Kanai A, Inaba T, Tanaka S, Chayama K.
  • Journal Title: Hepatology 2011 Volume: 54 Pages: 781-788
  • DOI: doi:10.1002/hep.24460
  • Peer Reviewed
• [Journal Article] Impact of viral amino acid substitutions and host interleukin-28b polymorphism on replication and susceptibility to interferon of hepatitis C viru (2011)
  • Author(s): Hiraga N, Abe H, Imamura M, Tsuge M, Takahashi S, Hayes CN, Ochi H, Tateno C, Yoshizato K, Nakamura Y, KamataniN, Chayama K.
  • Journal Title: Hepatology 2011 Volume: 54 Pages: 764-771
  • DOI: doi:10.1002/hep.24453.
  • Peer Reviewed
• [Journal Article] HCV substitutions and IL28B polymorphisms on outcome of peg-interferon plus ribavirin combination therapy (2011)
  • Author(s): Hayes CN, Kobayashi M, Akuta N, Suzuki F, Kumada H, Abe H, Miki D, Imamura M, Ochi H, Kamatani N, Nakamura Y, Chayama K.
  • Journal Title: Gut 2011 Volume: 60 Pages: 261-267
  • DOI: doi:10.1136/gut.2010.223495
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism in activated Cdc42 associated tyrosine kinase 1influences the interferon therapy in hepatitis C patients (2011)
  • Author(s): Fujimoto Y, Ochi H, Maekawa T, Abe H, Hayes CN, Kumada H, Nakamura Y, Chayama K.
  • Journal Title: J Hepatol 2011 Volume: 54 Pages: 629-639
  • DOI: doi:10.1016/j.jhep.2010.07.021
  • Peer Reviewed
• [Journal Article] IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1hepatitis C (2011)
  • Author(s): Chayama K, Hayes CN, Abe H, Miki D, Ochi H, Karino Y, Toyota J, Nakamura Y, Kamatani N, Sezaki H, Kobayashi M, Akuta N, Suzuki F, Kumada H
  • Journal Title: J Infect Dis 2011 Volume: 204 Pages: 84-93
  • DOI: doi:10.1093/infdis/jir210.
  • Peer Reviewed
• [Journal Article] ME3738 enhances the effect of interferon and inhibits hepatitis C virus replication both in vitro and in vivo (2011)
  • Author(s): Abe H, Imamura M, Hiraga N, Tsuge M, Mitsui F, Kawaoka T, Takahashi S, Ochi H, Maekawa T, Hayes CN, Tateno C, Yoshizato K, Murakami S, Yamashita N, Matsuhira T, Asai K, Chayama K
  • Journal Title: J Hepatol 2011 Volume: 55 Pages: 11-18
  • DOI: doi:10.1016/j.jhep.2010.10.017.
  • Peer Reviewed
• [Journal Article] IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy (2011)
  • Author(s): Abe H, Hayes CN, Ochi H, Maekawa T, Tsuge M, Miki D, Mitsui F, Hiraga N, Imamura M, Takahashi S, Kubo M, Nakamura Y, Chayama K.
  • Journal Title: Hepatol 2011 Volume: 54 Pages: 1094-1101
  • DOI: doi:10.1016/j.jhep.2010.09.019
  • Peer Reviewed
• [Journal Article] Long-term use of entecavir in nucleoside-naive Japanese patients with chronichepatitis B infection (2010)
  • Author(s): Yokosuka O, Takaguchi K, Fujioka S, Shindo M, Chayama K, Kobashi H, Hayashi N, Sato C, Kiyosawa K, Tanikawa K, Ishikawa H, Masaki N, Seriu T, Omata
  • Journal Title: J Hepatol 2010 Volume: 52 Pages: 791-799
  • DOI: doi:10.1016/j.jhep.2009.12.036.
  • Peer Reviewed
• [Journal Article] HBx protein is indispensable for development of viraemia in human hepatocyte chimericmice mice (2010)
  • Author(s): Tsuge M, Hiraga N, Akiyama R, Tanaka S, Matsushita M, Mitsui F, Abe H, Kitamura S, Hatakeyama T, Kimura T, Miki D, Mori N, Imamura M, Takahashi S, Hayes CN, Chayama K.
  • Journal Title: J Gen Virol 2010 Volume: 91 Pages: 1854-1864
  • DOI: doi:10.1099/vir.0.019224-0.
  • Peer Reviewed
• [Journal Article] IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis Cvirus genotype 2a/ 2b chimeric clones (2010)
  • Author(s): Suda G, Sakamoto N, Itsui Y, Nakagawa M, Tasaka-Fujita M, Funaoka Y, Watanabe T, Nitta S, Kiyohashi K, Azuma S, Kakinuma S, Tsuchiya K, Imamura M, Hiraga N, Chayama K, Watanabe M
  • Journal Title: Virology 2010 Volume: 407 Pages: 80-90
  • DOI: doi:10.1016/j.virol.2010.07.041
  • Peer Reviewed
• [Journal Article] ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy-a genome-wide study of Japanese HCV virus patients (2010)
  • Author(s): Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Kubo M, Tsunoda T, Hayes CN, Kumada H, Nakamura Y, Chayama K
  • Journal Title: Gastroenterology 2010 Volume: 139 Pages: 1190-1197
  • DOI: doi:10.1053/j.gastro.2010.06.071.
  • Peer Reviewed
• [Journal Article] Cellculture and in vivo analyses of cytopathic hepatitis C virus mutants (2010)
  • Author(s): Mishima K, Sakamoto N, Sekine-Osajima Y, Nakagawa M, Itsui Y, Azuma S, Kakinuma S, Kiyohashi K, Kitazume A, Tsuchiya K, Imamura M, Hiraga N, Chayama K, Wakita T, Watanabe M
  • Journal Title: Virology 2010 Volume: 405 Pages: 361-369
  • DOI: doi:10.1016/j.virol.2010.06.020.
  • Peer Reviewed
• [Journal Article] Practical evaluation of a mouse with chimeric human liver model for hepatitis C virus infection using an NS3-4A protease inhibitor using an NS3-4A protease inhibitor (2010)
  • Author(s): Kamiya N, Iwao E, Hiraga N, Tsuge M, Imamura M, Takahashi S, Miyoshi S, Tateno C, Yoshizato K, Chayama K
  • Journal Title: J Gen Virol 2010 Volume: 91 Pages: 1668-1677
  • DOI: doi:10.1099/vir.0.019315-0.
  • Peer Reviewed
• [Journal Article] Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin (2010)
  • Author(s): Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Chayama K, Nakamura Y, Kumada H
  • Journal Title: Hepatology 2010 Volume: 52 Pages: 421-429
  • DOI: doi:10.1002/hep.23690
  • Peer Reviewed
• [Journal Article] Common variation of IL28 affectsgamma-GTP levels and inflammation ofthe liver in chronically infectedhepatitis C virus patients (2010)
  • Author(s): Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, Mitsui F, Hiraga N, Imamura M, Takahashi S, Ohishi W, Arihiro K, Kubo M, Nakamura Y, ChayamaK
  • Journal Title: Hepatol 2010 Volume: 53 Pages: 439-443
  • DOI: doi:10.1016/j.jhep.2010.03.022.
  • Peer Reviewed
• [Presentation] Dual Oral Combination Therapy with the NS5A Inhibitor BMS-790052 and the NS3 Protease Inhibitor BMS-650032 Achieved 90% Sustained Virologic Response(SVR12) in HCV Genotype 1b-Infected Null Responders (2011)
  • Author(s): Chayama Kazuaki
  • Organizer: The 62nd Annual Meeting of American Association for the Study of Liver Diseases(AASLD)
  • Place of Presentation: San Francisco U. S. A.
  • Year and Date: 2011-11-07