Expression data from transgenic mice (3 mo) inducibly expressing human alpha1-antitrypsin in the liver. Mus musculus

In the classical form of α1antitrypsin deficiency a mutant protein accumulates in a polymerized form in the ER of liver cells causing liver damage and carcinogenesis by a gain-of-toxic function mechanism. Recent studies have indicated that the accumulation of mutant α1antitrypsin Z in the ER specifically activates the autophagic response but not the unfolded protein response and that autophagy plays a critical role in disposal of insoluble α1antitrypsin Z. In this study, we used genomic analysis of the liver in a novel transgenic mouse model with inducible expression to screen for changes in gene expression that would potentially define how the liver responds to accumulation of this mutant protein. Keywords: genomic analysis, alpha1-antitrypsin deficiency, comparative study, adult animals, inducible expression, liver specific Overall design: Liver RNA from adult (3 mo old) male mice inducibly expressing human alpha1-antitrypsin wild type (M) or mutant (Z) form exclusively in the liver was subjected to genomic analysis. Groups: mutant AAT (Z), wild type AAT (M), expressing (4), non-expressing (1), wild type littermates (WT); 3 biological replicates/each group