Previous studies indicate that a variety of different genes can be expressed and regulated appropriately in different transgenic animal model systems. Transgenic model systems have been used successfully to study the role of oncogenes in tumorigenesis. From transgenic animal data and in vitro studies it has been demonstrated that oncogenesis is a multistep process and is composed of a series of steps required to develop a normal cell into a malignant tumor. In vitro studies have shown that myc and ras cooperate to transform primary cells into a transformed cell and can also induce tumors in nude mice. Similar cooperative effect between myc and ras has also been demonstrated in transgenic animals. In an effort to investigate the role of ets-1 and ets-2 during development, differentiation and oncogenesis, we decided to generate transgenic mice that contain integrated copies of ets-1 or ets-2 genes linked to either normal or heterologous promoters that may be induced by steroids or heavy metals. The linking of ets genes to heterologous promoter will probably lead to expression of ets in an inappropriate tissue; this approach will allow us to study the consequences of ets expression in different cell types and tissue types. The ets-2 transgenic mice were developed by microinjecting the mouse ets-2 gene linked to the metallothionein promoter. We currently have more than 100 ets-2 transgenic mice developed from the single founder animal. By Northern blot analysis we have found that the transgenic mice express the ets-2 transgene only in testis. Currently, we are employing PCR technology to examine the other tissues for ets-2 transgene expression. In normal mice, the ets-2 gene is expressed at low levels in almost every tissue and at high levels only in thymus. The ets-2 transgenic mice we have developed will allow us to study the effect of high levels of ets-2 expression in mouse testis.
