Comprehensive characterization of hepatic inflammatory changes in a mouse model of alpha-1 antitrypsin deficiency. Comprehensive characterization of hepatic inflammatory changes in a mouse model of alpha-1 antitrypsin deficiency

In this study, we sought to thoroughly characterize the liver pathophysiology of a human transgenic mouse model for alpha-1 antitrypsin deficiency (AATD) with a strong manifestation of AATD-mediated liver disease. Male and female transgenic mice for normal variant human alpha-1 antitrypsin (Pi*M) and mutant human alpha-1 antitrypsin (Pi*Z) at 3 and 6 months of age with a C57BL/6J background were subjected to study. The progression of hepatic accumulation of mutant alpha-1 antitrypsin (ZAAT), hepatocyte injury, steatosis, liver inflammation and fibrotic features of this mouse model were monitored by performing an in vivo study. Overall design: This study was performed with approval from the University of Florida Institutional Animal Care and Use Committee with strict adherence to the Guide for Care and Use of Laboratory Animals (NIH, 86-23). Transgenic Pi*Z and Pi*M were maintained on a C57BL/6J background. Mice were provided food, water and 12:12 hour dark:light cycles in a barrier facility. Intraperitoneal injection of lipopolysaccharide (LPS, InvivoGen, San Diego, CA) at a dose of 0.5ug LPS/g of body mass was performed 16 hours prior to euthanasia.