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PMID: 8290572 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 2 ·1994-01-18 ·Pages 614-8

Toyonaga T, Hino O, Sugai S, Wakasugi S, Abe K, Shichiri M, Yamamura K

Abstract

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.

Related Genes
IFN-gamma SAP
MeSH Terms
Alanine Transaminase/blood Animals Aspartate Aminotransferases/blood Disease Models, Animal Female Gene Expression Hepatitis, Chronic/genetics,immunology,pathology Histocompatibility Antigens Class II/metabolism Interferon-gamma/biosynthesis,blood,genetics Liver/immunology,pathology Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Promoter Regions, Genetic Serum Amyloid P-Component/genetics
Chemicals
Histocompatibility Antigens Class II Serum Amyloid P-Component Interferon-gamma Aspartate Aminotransferases Alanine Transaminase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Toyonaga T
Department of Developmental Genetics, Kumamoto University School of Medicine, Japan.
Hino O
Sugai S
Wakasugi S
Abe K
Shichiri M
Yamamura K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.2.614
Published
1994-01-18
Pages
614-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42999
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.91.2.614 PMC Full Text View journal details
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