Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein

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Title
Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein
Author(s)
Dae Yeul Yu; Hyung Bae Moon; Jin Kyong Son; Sang Kyun Jeong; Seong Lan Yu; Hee Sik Yoon; Yong Mahn Han; Chul Sang Lee; Jung Sun ParkChul Ho Lee; Byung Hwa Hyun; Seishi Murakami; Kyung Kwang Lee
Bibliographic Citation
Journal of Hepatology, vol. 31, no. 1, pp. 123-132
Publication Year
1999
Abstract
Background/Aims: Chronic infection with hepatitis B virus is a high- risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors. Methods: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6xDBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations. Results: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei. Conclusion: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena.
Keyword
HBV X-genehepatic tumorsproliferating cell nuclear antigentransgenic mice
ISSN
0168-8278
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S0168-8278(99)80172-X
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
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