Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver.

作者：Tomomi Toyonaga, Okio Hino, S Sugai, Sunao Wakasugi, Kuniya Abe, Masayoshi Shichiri, K Yamamura · 发表于：Proceedings of the National Academy of Sciences · 年份：1994 · DOI：10.1073/pnas.91.2.614 · 被引用次数：214 · 研究领域：Diabetes and associated disorders、Viral gastroenteritis research and epidemiology、Liver physiology and pathology

Interferon-gamma may play an important role in the immune response and in inflammatory diseases, including chronic active hepatitis. To understand the role of interferon-gamma in the regulation of inflammation and to establish a mouse model of chronic active hepatitis, we produced transgenic mice in which the mouse interferon-gamma gene was regulated by a liver-specific promoter, the serum amyloid P component gene promoter. Four transgenic mouse lines were generated, and two of these lines expressed mRNA of interferon-gamma in the liver. Levels of serum transaminases increased gradually as a function of age and were significantly higher than those of interferon-gamma-negative littermates after 4 weeks after birth. One transgenic mouse line showed a histology of chronic active hepatitis similar to that found in human patients, although cirrhotic changes such as fibrosis were scarce. Thus, the liver-specific production of interferon-gamma is sufficient to induce chronic inflammatory disease and this mouse is a transgenic model of chronic active hepatitis.