CHRONIC ACTIVE HEPATITIS IN TRANSGENIC MICE EXPRESSING INTERFERON-GAMMA IN THE LIVER
CHRONIC ACTIVE HEPATITIS IN TRANSGENIC MICE EXPRESSING INTERFERON-GAMMA IN THE LIVER
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DOI：
10.1073/pnas.91.2.614
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发表时间：
1994-01-18
影响因子：
11.1
通讯作者：
YAMAMURA, K
中科院分区：
文献类型：
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作者：
TOYONAGA, T;HINO, O;YAMAMURA, K
干扰素-γ可能在免疫应答和炎症性疾病中起重要作用，包括慢性活动性肝炎。为了了解干扰素-γ在炎症调节中的作用，并建立慢性活动性肝炎的小鼠模型，我们生产了转基因小鼠，其中小鼠干扰素-γ基因由肝脏特异性启动子（血清淀粉样蛋白P组分基因启动子）调节。产生了四个转基因小鼠品系，其中两个品系在肝脏中表达干扰素-γ的mRNA。血清转氨酶水平随着年龄的增长而逐渐升高，出生后4周后显著高于干扰素-γ阴性的同窝仔。一个转基因小鼠系表现出与人类患者相似的慢性活动性肝炎组织学，尽管肝纤维化等肝硬化变化很少。因此，干扰素-γ的肝脏特异性产生足以诱导慢性炎性疾病，并且该小鼠是慢性活动性肝炎的转基因模型。
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.