Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion

Background/Aims: The mechanisms underlying alcohol-induced liver injury are not fully elucidated. An approach in this direction would consist of an all-inclusive assessment of gene expression in the liver. The purpose of this study was to perform a comprehensive analysis of gene expression in the livers of mice treated with ethanol by means of intragastric infusion. Methods: An ethanol- or glucose-enriched liquid diet was fed to animals for 4 weeks via a long-term gastrostomy catheter. The animals were killed and plasma alanine:2-oxoglutarate aminotransferase (ALT) assay, liver histology and total RNA analysis by microarray gene technology were performed. Results: Alcohol increased ALT, induced steatosis, necrosis and inflammation. A total of 12,423 genes were analyzed for expression out of which 4867 were expressed by the liver. Alcohol repressed expression of 11 genes, induced expression of 13 genes, and up- or down-regulated expression of 44 and 42 genes > 2-fold, respectively. Gene expression analysis identified several genes that have not previously been tested for alcohol effects. Conclusions: This study: (i) expands the knowledge of mechanism(s) of action of ethanol; (ii) indicates novel pathways of ethanol action on the liver, and (iii) illustrates the utility of microarray gene analysis in hepatology research. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.