Global expression screens, accomplished by microarray analysis, provide a systematic approach for identifying changes in gene expression between different tissues and/or physiologic states within a given tissue. We propose to use microarray technologies to identify genes that are differentially expressed between nicotine-sensitive and insensitive strains of mice as well as mice in which specific genes have been altered by homologous recombination. We expect that these studies will identify unexpected genes and/or pathways involved in nicotine addiction and response. We propose to exploit an existing microarray facility to accomplish these goals. This facility uses high throughput robotics protocols to prepare DNA for deposition and for microarray production. Integrated relational databases assure that the integrity of the clone collections is maintained. Current collections include all of the yeast ORFs, 40,000 human genes, 2,000 drosophila genes and 15,000 mouse genes. For this proposal, the facility will function as a scientific core, providing mouse microarray production, interrogation and data analysis for Projects 2 and 3.