Differential gene expression in ATZ-globule-free and ATZ-globule-containing hepatocytes in PIZ mouse liver. Mus musculus

Alpha-1-antitrypsin deficiency is a disease of the liver and lung where accumulation of misfolded ATZ protein forms large protein aggregates or globules that result in significant cellular stess. From Birth to 2 months of age, virtually every hepatocyte has numerous globules of the mutant ATZ protien. At 2 months of age small colonies of globule free hepatocytes arise and over time the liver becomes largely globule free. this analysis aims to identify differential gene expression profiles in the globule free vs the globule containing cells to idenitfy key factors and pathways regulating clearance of the mutant ATZ protien. We used Laser Capture Microdisection to isolate RNA from ATZ-globule-free hepatocytes and ATZ-globule-containing hepatocytes and subjected them to microarray analysis to detail the differential global gene expression profiles. Overall design: PIZ mice 3 months of age were sacrificed and their livers were mounted in OCT compound and fresh frozen in methylbutane. Liver sections were placed on slides and counterstained with Cresyl Violet to visualize globules. The slides were then subjected to laser capture micro-disection of globule free and globule containing areas.