The MAP kinase cascade is a signal transduction pathway which has been extensively studied by our lab; ERK1 and ERK2 are central molecules within this cascade. These two proteins are highly related, showing 90% sequence similarity at the nucleotide level, with the regions of non-identity restricted to the amino terminus of the proteins. In an attempt to understand the functional role of these kinases, we have taken a genetic approach by using gene targeting techniques to remove either ERK1 or ERK2. We have generated ERK1 KO animals which show a mild T-cell phenotype. Based on reports of embryonic lethality in the ERK2 KO, we have generated a floxed ERK2 line which will be used to mate with various Cre transgenics. We are most interested in lines which have neuronal Cre expression.