The Ets family of transcription factors/protooncogenes are defined by their common DNA binding motif, GGAA. Many members of the Ets family have been identified and their biochemical properties have been studied in vitro. Our work has focused on determining the expression pattern for Ets genes during mouse development and understanding regulatory mechanisms which determine the tissue-specific and developmentally appropriate expression of these genes. We have identified genomic regions of the Ets-1 gene which may be important for directing expression to vascular elements derived from the neural crest. We are also interested in using transgenic mouse techniques to further elucidate functional roles for the Ets genes, in particular, Ets-1 and Ets-2. These genes are being overexpressed in transgenic mice using various regulatory elements to direct the overexpression of Ets-1 and Ets-2 to multiple tissues including the thymus, endothelium and cartilage. Embryonic stem (ES) cells containing null mutants of Ets-1 have been created and are being used to create mice carrying null mutants of the Ets-1 gene. The roles of Ets family members are being investigated in relation to the expression of other lymphoid genes, in mouse models of autoimmunity, as well as in the development of prostate and mammary adenocarcinomas.