Functional analyses of the murine Ets-1 and Ets-2 transcriptional factors/ oncogenes are being conducted utilizing the transgenic mouse system. The trans-genic studies involve in vivo analysis of: 1) cis-regulatory elements of the Ets-1 and Ets-2 genes; 2) misexpression of the Ets-1 and Ets-2 cDNAs; and 3) null mutation of the Ets-1 and Ets-2 genes. Several gene hybrid constructs have been created containing various elements of the Ets regulatory regions fused to the lacZ reporter gene. Various constructs to target the overexpression of Ets cDNAs to multiple tissue types have also been generated. Several constructs which disrupt the Ets- 1 locus through targeted homologous recombination in embryonic stem (ES) cells have been created. Results of these multiple approaches in analyzing the Ets genes in transgenic mice should provide a more thorough understanding of the regulation and function of this important set of transcription factors and oncogenes.