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World J Hepatol. Dec 8, 2015; 7(28): 2834-2840
Published online Dec 8, 2015. doi: 10.4254/wjh.v7.i28.2834
Contributions of transgenic mouse studies on the research of hepatitis B virus and hepatitis C virus-induced hepatocarcinogenesis
Shogo Ohkoshi, Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa, Masahiko Yano
Shogo Ohkoshi, Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa, Department of Internal Medicine, School of Life Dentistry at Niigata, the Nippon Dental University, Niigata-city 951-8580, Japan
Masahiko Yano, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences Niigata University, Niigata-city 951-8520, Japan
Author contributions: All authors contributed to this manuscript.
Supported by A Grant-in-Aid for Scientific Research (C) (25461012 to Shogo Ohkoshi) from the Japan Society for the Promotion of Science (JSPS).
Conflict-of-interest statement: The authors do not have any commercial affiliation or consultancy that could be construed as a conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shogo Ohkoshi, MD, PhD, Department of Internal Medicine, School of Life Dentistry at Niigata, the Nippon Dental University, 1-8 Hamaura-Cho, Chuo-ku, Niigata-city 951-8580, Japan. okoshi@ngt.ndu.ac.jp
Telephone: +81-25-2118243 Fax: +81-25-2671582
Received: July 22, 2015
Peer-review started: July 27, 2015
First decision: September 22, 2015
Revised: September 28, 2015
Accepted: November 24, 2015
Article in press: November 25, 2015
Published online: December 8, 2015
Processing time: 133 Days and 2.1 Hours
Abstract

Transgenic mouse technology has enabled the investigation of the pathogenic effects, including those on development, immunological reactions and carcinogenesis, of viral genes directly in living organism in a real-time manner. Although viral hepatocarcinogenesis comprises multiple sequences of pathological events, that is, chronic necroinflammation and the subsequent regeneration of hepatocytes that induces the accumulation of genetic alterations and hepatocellular carcinoma (HCC), the direct action of viral proteins also play significant roles. The pathogenesis of hepatitis B virus X and hepatitis C virus (HCV) core genes has been extensively studied by virtue of their functions as a transactivator and a steatosis inducer, respectively. In particular, the mechanism of steatosis in HCV infection and its possible association with HCC has been well studied using HCV core gene transgenic mouse models. Although transgenic mouse models have remarkable advantages, they are intrinsically accompanied by some drawbacks when used to study human diseases. Therefore, the results obtained from transgenic mouse studies should be carefully interpreted in the context of whether or not they are well associated with human pathogenesis.

Keywords: Transgenic mouse; Hepatocarcinogenesis; Hepatitis C virus; Hepatitis B virus X; Hepatitis B virus; Hepatitis C virus core protein; Steatosis

Core tip: Transgenic technology offers researchers several advantages over in vitro experiments, including the ability to trace the pathogenic effects of viral genes in living organisms. Transgenic mouse studies have provided evidence that the direct action of viral genes, especially the genes encoding hepatitis B virus X and hepatitis C virus core proteins, is involved in hepatocarcinogenesis. However, such results should be considered carefully as transgenic mouse experiments have intrinsic advantages and drawbacks. As such, the results including phenotypes and molecular mechanisms from transgenic mouse studies must always be verified by comparing them to those of human studies for evidence of an association.