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Hepatitis B virus transgenic mouse model of chronic liver disease

Nature Medicine volume 5, pages 907–912 (1999)Cite this article

Abstract

A model for hepatitis B virus-associated chronic liver disease has been made using cloned hepatitis B virus DNA as a transgene in a severe combined immunodeficient host. These mice consistently support virus gene expression and replication. After adoptive transfer of unprimed, syngeneic splenocytes, these mice cleared virus from liver and serum, and developed chronic liver disease. This model will permit identification of the host and virus contributions to chronic liver disease in the absence of tolerance.

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Figure 1: Evidence of viral replication in serum and liver of HBV transgenic SCID mice.
Figure 2: Concentration of HBV DNA in the sera of transgenic mice.
Figure 3: Detection of viral antigens in the serum and liver of transgenic mice.
Figure 4: ALT and HBV markers in the blood of adoptively transferred mice.
Figure 5: Hematoxylin and eosin staining of livers from transgenic mice recovered 35 weeks after the adoptive transfer of 1 × 107 splenocytes.
Figure 6: HBV gene expression and replication in the liver before and 35 weeks after adoptive transfer.

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Acknowledgements

The authors thank C. Calkins and L. Eisenlohr for discussions, and J. Song for assisting in screening mice for virus. This work was supported by NIH grants CA48656 and CA66971, and by a grant from the Alcoholic Beverage Medical Research Foundation to M.A.F. This work was also supported by a pilot project from AA07186 to E. Rubin. The Kimmel Cancer Center Transgenic and Knockout Mouse Facility is supported, in part, by NIH grant CA56036.

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Author notes

  1. Judith L. Morgan

    Present address: Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia, Pennsylvania, 19111, USA

  2. Frank H. Michaels

    Present address: OraGen, 3600 Inverness Drive, Chevy Chase, Maryland, 20815

Authors and Affiliations

  1. Department of Pathology, Anatomy and Cell Biology Thomas Jefferson University, Room 222 Alumni Hall, 1020 Locust Street, Philadelphia, 19107, Pennsylvania, USA

    Jonathan Larkin, Marcy Clayton, Bill Sun, Claire E. Perchonock & Mark A. Feitelson

  2. Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, USA

    Judith L. Morgan, Linda D. Siracusa, Frank H. Michaels & Mark A. Feitelson

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Correspondence to Mark A. Feitelson.

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Larkin, J., Clayton, M., Sun, B. et al. Hepatitis B virus transgenic mouse model of chronic liver disease. Nat Med 5, 907–912 (1999). https://doi.org/10.1038/11347

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