PMID:12165491

Citation	Bettini, M, Xi, H, Milbrandt, J and Kersh, GJ (2002) Thymocyte development in early growth response gene 1-deficient mice. J. Immunol. 169:1713-20
Abstract	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.
Links	PubMed
Keywords	Animals; CD4-Positive T-Lymphocytes/cytology; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/metabolism; CD8-Positive T-Lymphocytes/cytology; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/metabolism; Cell Differentiation; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/immunology; Early Growth Response Protein 1; Gene Expression Regulation, Developmental; Genes, T-Cell Receptor; Genes, bcl-2; Immediate-Early Proteins; Inhibitor of Differentiation Proteins; Leukocyte Count; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mice, Transgenic; Mitogen-Activated Protein Kinases/metabolism; Neoplasm Proteins; Signal Transduction; T-Lymphocytes/cytology; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/immunology; Up-Regulation
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