2 DISTINCT STEPS DURING THYMOCYTE MATURATION FROM CD4(-)CD8(-)TO CD4(-RESPONSE (EGR)-1 TRANSGENIC MICE WITH A RECOMBINASE-ACTIVATING GENE-DEFICIENT BACKGROUND()CD8(+) DISTINGUISHED IN THE EARLY GROWTH)

The early growth response (Egr)-1 is a zinc finger-containing transcri ption factor belonging to the immediate-early genes. Its expression in CD4/CD8 double negative (DN) immature thymocytes suggests that Egr-1 expression may be involved in early thymocyte development. In transgen ic mice overexpressing Egr-1 in a recombinase-activating gene-deficien t background, thymocytes bypassed the block at the CD25(+)CD44(-) DN s tage and matured to the immature CD8 single-positive (ISP) cell stage, but not further to the CD4/CD8 double-positive (DP) cell stage. When these mice were irradiated, thymocytes did develop to the DP stage, su ggesting transcriptional induction of additional genes by irradiation that are required to promote thymocyte development from the ISP to the DP stage. These results provide genetic evidence for two distinct ste ps during early thymocyte development from the CD25(+)CD44(-) DN to th e DP stage. The first step, from the CD25(+)CD44(-) DN to the ISP stag e, can be entirely promoted by overexpression of Egr-1.