Two Distinct Steps during Thymocyte Maturation from CD4(−)CD8(−) to CD4(+)CD8(+) Distinguished in the Early Growth Response (Egr)-1 Transgenic Mice with a Recombinase-activating Gene–Deficient Background

The early growth response (Egr)-1 is a zinc finger–containing transcription 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 transgenic mice overexpressing Egr-1 in a recombinase-activating gene–deficient background, thymocytes bypassed the block at the CD25(+)CD44(−) DN stage 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, suggesting 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 steps during early thymocyte development from the CD25(+)CD44(−) DN to the DP stage. The first step, from the CD25(+)CD44(−) DN to the ISP stage, can be entirely promoted by overexpression of Egr-1.