Summary
We produced transgenic mice by microinjecting a partially duplicated copies of hepatitis B virus (HBV) gene into fertilized eggs of C57BL/6 mice. One mouse was a high producer of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the serum. All offspring carrying HBV DNA were positive for both antigens in the serum. The HBV DNA was expressed in liver-and kidney-specific manner. The normal process of HBV replication, including the packaging of the pregenome 3.5-kb RNA into a nucleocapsid, the reverse-transcription of the complete minus strand DNA, and the release of Dane particles into the serum before the completion of synthesis of plus strand, occurred in the liver of these transgenic mice. These results suggest that the species specificity of HBV infection is not due to the inability to replicate in nonnatural host but to the lack of receptors or factors needed for virus adsorption and internalization. The founder mouse is now 19 months of age but shows no clinical or pathological change, suggesting that HBV itself is not cytopathic.
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References
Araki K, Miyazaki J, Hino O, et al: Expression and replication of hepatitis B virus genome in transgenic mice. Proc Natl Acad Sci USA 1989;86:207–211
Yamamura K, Kikutani H, Takahashi N, et al: Introduction of human γ1 immunoglobulin genes into fertilized mouse eggs. J Biochem 1984;96:357–363
Southern EM: Detection of specific sequences among fragments separated by gel electrophoresis. J Mol Biol 1975;98:503–517
Maniatis T, Fritsch EF, Sambrook J: Molecular cloning. Cold Spring Harbor Laboratory, New York. 1982;187–206
Tiollais P, Pourcel C, Dejean A: The hepatitis B virus. Nature 1985;317:489–495
Yamamura K, Tsurimoto T, Ebihara T, et al: Methylation of hepatitis B virus DNA and liver-specific supression of RNA production in transgenic mouse. Jpn J Cancer Res 1987;78:681–688
Araki K, Miyazaki J, Tsurimoto T, et al: Demethylation by 5-azacytidine results in the expression of hepatitis B virus surface antigen in transgenic mice. Jpn J Cancer Res 1989;80:295–298
Farza H, Hadchouel M, Scotto J, et al: Replication and gene expression of hepatitis B virus in a transgenic mouse that contains the complete viral genome. J Virol 1988;62:4144–4152
Shaul Y, Rutter WJ, Laub O: A human hepatitis B viral enhancer element. EMBO J 1985;4:427–430
Chisari FV, Pinkert CA, Milich DR, et al: A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science 1985;230:1157–1160
Babinet C, Farza H, Morello D, et al: Specific expression of hepatitis B virus surface antigen (HBsAg) in transgenic mice. Science 1985;230:1160–1163
Burk RD, DeLoia JA, ElAwady MK, et al: Tissue preferential expression of the hepatitis B virus (HBV) surface antigen gene in two lines of HBV transgenic mice. J Virol 1988;62:649–654
Chisari FV, Filippi P, Buras J, et al: Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci USA 1987;84: 6909–6913
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This work was supported by a Grant-in-Aid for Cancer Research from the Japanese Minister of Education, Science and Culture. We thank Ms.R.Kitamura for assistance in the preparation of this manuscript.
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Yamamura, Ki., Araki, K., Hino, O. et al. HBV production in transgenic mice. Gastroenterol Jpn 25 (Suppl 2), 49–52 (1990). https://doi.org/10.1007/BF02779928
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DOI: https://doi.org/10.1007/BF02779928