Thymocyte development in early growth response gene 1-deficient mice.
Early growth response gene 1 (Egr1) codes for a transcriptional regulator that contains a zinc-finger DNA binding domain. Egr1 expression is induced by a variety of extracellular stimuli including TCR-ligand interactions. Its pattern of expression in the thymus and dependence on ERK activation have led to speculation that it has a role in T cell development, but the exact nature of this role has been undefined. To more clearly define the role of Egr1 in thymocyte development, we have analyzed thymocytes from Egr1-deficient mice. We find that thymuses from Egr1-deficient mice contain twice as many cells as age-matched controls, and the increase in thymocyte number is apparent at the early CD4/CD8 double negative stage of development. Subsequent maturation to the CD4/CD8 double positive stage and survival of the double positive cells both appear normal in Egr1-deficient animals. We also find that Egr1 promotes positive selection of both CD4 and CD8 single positive cells without playing a major role in negative selection. Egr1 influences positive selection by enhancing expression of the helix-loop-helix inhibitor Id3 and the anti-apoptosis molecule bcl-2. Thus, Egr1 translates developmental signals into appropriate changes in gene expression at multiple stages of thymocyte development.
Bettini
Matthew
M
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Xi
Hongkang
H
Milbrandt
Jeffrey
J
Kersh
Gilbert J
GJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051766:Early Growth Response Protein 1; D018507:Gene Expression Regulation, Developmental; D019672:Genes, T-Cell Receptor; D019254:Genes, bcl-2; D017874:Immediate-Early Proteins; D051796:Inhibitor of Differentiation Proteins; D007958:Leukocyte Count; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009363:Neoplasm Proteins; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C075640:ID3 protein, human; D020928:Mitogen-Activated Protein Kinases