Comparative transcriptomics of models of lipid-associated disorders Disease phenotypes arise from complex interactions of organisms with their environments. While we have along history of associating genes and gene defects with a large array of diseases, a growing body of datasuggests that many disease phenotypes arise from the interactions of genes with their environments -including the genetic background in which those genes are expressed. The goal in this project is to explore these interactions using cDNA microarray technology, in conjunction with the characterization of mousephenotypes relevant to lipid-associated disorders, and to identify genes, pathways, and environmental factors that contribute to the development of the disease state.The overall goal of this component is to identify subsets of genes that are particularly relevant to the biology of lipid-associated disorders and to prioritize the information for further focused studies. We are concentrating our efforts on expression profiling using mouse models of lipid-associated disorders, comparative analyses of the generated profiles, and ChIP on chip assays. Specifically, we aim to: Develop a molecular atlas of wild-type and mutant mouse adipocytes. We have developed a mouse microarray and aim to enrich this array with an additional library and to conduct expression assays to establish a wild-type and mutant gene expression atlas of mouse adipocytes. Identify regulators involved in fat cell differentiation.We have established an in vitro adipocyte differentiation assay using calvariae calvariae cells of newborn mice (mesenchymal precursor cells) to identify genes important for adipocyte differentiation. We will compare transcriptional profiles of differentiating wild-type cells with differentiating cells from transgenic mice. Develop ChIP on chip (Chromatin immunoprecipitation on microarray). We aim to develop a mouse promoter microarray to identify target genes of key transcription factors selectedin the previous aims and in other subprojects.