Although clinical samples can provide considerable insight into the changes in cellular gene expression that occur during liver disease progression, they are not necessarily ideal for studies investigating the molecular mechanisms responsible for these changes. These types of studies typically require an animal model that can be experimentally manipulated. In this regard, research in the HCV field has been significantly enhanced by the development of a mouse model of HCV infection. This model, developed by Lorne Tyrrell and Norman Kneteman at the University of Alberta, Canada, is based on the severe combined immunodeficiency disorder (SCID)-beige/albumin (Alb)-urokinase plasminogen activator (uPA) transgenic mouse. Intrasplenic injection of freshly isolated human hepatocytes into these mice leads to the repopulation of the mouse liver with human hepatocytes. The result is a mouse containing a chimeric mouse-human liver and these animals can be persistently infected with a variety of HCV genotypes [15] . The chimeric mouse model provides a number of features that make it a useful system in which to study HCV-host interactions. Because groups of mice are transplanted with hepatocytes from different donors, we have the opportunity to analyze host-specific responses to HCV. In addition, the lack of an adaptive immune response in these animals makes it possible to distinguish between virus-mediated and immune-mediated effects on gene expression. Kathie Walters is using this model to characterize the host transcriptional response to HCV infection. Because liver samples from these animals typically have small percentages of contaminating mouse liver tissue, she first evaluated the level of cross-hybridization of mouse liver mRNA to the human probes present on the microarray [16] . The small set of genes identified (less than 2% of the genes present on the array) is either removed from subsequent data analysis or changes in the expression of these genes are validated using human-specific quantitative realtime PCR.