Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver.
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.
Toyonaga
T
T
Department of Developmental Genetics, Kumamoto University School of Medicine, Japan.
Hino
O
O
Sugai
S
S
Wakasugi
S
S
Abe
K
K
Shichiri
M
M
Yamamura
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006521:Hepatitis, Chronic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D000683:Serum Amyloid P-Component / Q000235:genetics
D000949:Histocompatibility Antigens Class II; D000683:Serum Amyloid P-Component; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase