Efficient Conditional Transgene Expression in Hepatitis C Virus cDNA Transgenic Mice Mediated by the Cre/loxP System

Conditional gene expression has greatly facilitated the examination of the functions of particular gene products. Using the Cre/loxP system, we developed efficient conditional transgene activation of hepatitis C virus (HCV) cDNA (nucleotides 294–3435) in transgenic mice. Efficient recombination was...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-04, Vol.273 (15), p.9001-9006
Main Authors: Wakita, Takaji, Taya, Choji, Katsume, Asao, Kato, Junko, Yonekawa, Hiromichi, Kanegae, Yumi, Saito, Izumu, Hayashi, Yukiko, Koike, Morio, Kohara, Michinori
Format: Article
Language:English
Subjects:
Adenoviridae - enzymology
Adenoviridae - genetics
Animals
DNA, Complementary
Gene Expression Regulation
Gene Transfer Techniques
Hepacivirus - genetics
Hepacivirus - growth & development
Hepatitis B Core Antigens - biosynthesis
Hepatitis B Core Antigens - blood
Integrases - biosynthesis
Integrases - metabolism
Liver - pathology
Liver - virology
Mice
Mice, Transgenic
Organ Specificity
Polymerase Chain Reaction
Viral Proteins
Virus Activation
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Summary:Conditional gene expression has greatly facilitated the examination of the functions of particular gene products. Using the Cre/loxP system, we developed efficient conditional transgene activation of hepatitis C virus (HCV) cDNA (nucleotides 294–3435) in transgenic mice. Efficient recombination was observed in transgenic mouse liver upon intravenous administration of adenovirus that expresses Cre DNA recombinase. After transgene activation, most hepatocytes were stained with anti-core polyclonal antibody, and 21-, 37-, and 64-kDa proteins were detected by Western blot analysis in liver lysates using anti-core, E1, and E2 monoclonal antibodies, respectively. Serum core protein was detected in transgenic mice 7 days after transgene activation with concurrent increases in serum alanine aminotransferase levels. Subsequently, an anti-core antibody response was detected 14 days after infection. Furthermore, a CD4 and CD8 positive cell depletion assay normalized both the serum alanine aminotransferase increases and pathological changes in the liver. These results suggest that HCV proteins are not directly cytopathic and that the host immune response plays a pivotal role in HCV infection. Thus, this HCV cDNA transgenic mouse provides a powerful tool with which to investigate the immune responses and pathogenesis of HCV infection.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.15.9001