References
Query Results -- Details
MGI Accession ID: MGI:3790276
J Number: J:135035
Other Accession IDs:
Title: IFNgamma expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface protein-accumulating transgenic livers.
Authors: Reifenberg K; Hildt E; Lecher B; Wiese E; Nusser P; Ott S; Yamamura K; Rutter G; Lohler J
Journal: Liver Int
Volume: 26
Issue: 8
Date: 2006 Oct
Year: 2006
Pages: 986-93
Review Status: Peer Reviewed
Abstract:
BACKGROUND/AIMS: Interferon gamma (IFNgamma) controls hepatitis B virus replication. As systemic application may cause severe adverse effects, approaches of liver-directed IFNgamma gene therapy may represent an attractive alternative for treatment of chronic viral hepatitis B and thus needs testing in vivo in suitable animal models. METHODS: We therefore crossbred Alb-1HBV transgenic mice overexpressing the large HBV surface protein (LHBs) in their livers and developing LHBs storage disease and ground glass hepatocyte appearance with SAP-IFNgamma transgenic animals previously shown to exhibit constitutive hepatic IFNgamma expression, and analyzed the resulting double-transgenic offspring. RESULTS: We found that IFNgamma coexpression significantly reduced hepatic LHBs expression and thereby inhibited hepatocellular LHBs storage disease and ground glass hepatocyte appearance. The beneficial antiviral IFNgamma effects as observed in Alb1-HBV SAP-IFNgamma double-transgenic livers were associated with significantly elevated serum ALT concentrations, massive mononuclear cell infiltrates, appearance of Councilman bodies, and increased alpha-PARP (poly(ADP-ribose) polymerase cleavage). CONCLUSIONS: Exacerbation of hepatic necroinflammation and increased hepatocellular apoptosis rate in IFNgamma-expressing Alb1-HBV transgenic livers suggest that special precautions be taken for testing approaches of liver-specific IFNgamma expression in patients with chronic hepatitis B.
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