Defective activation and survival of T cells lacking the Ets-1 transcription factor.
The Ets-1 proto-oncogene is a member of the Ets family of eukaryotic transcription factors. Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals. Ets-1 is preferentially expressed at high levels in B and T cells of adult mice and is regulated during both thymocyte development and T-cell activation. To study the role of Ets-1 in T-cell development and function we have used the RAG-2-/- complementation system and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene (Ets-1-/-). Ets-1-/(-)-RAG-2-/- chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells. Ets-1-/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-alpha/beta. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro. These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.
Muthusamy
N
N
Department of Medicine, University of Chicago, Illinois 60637, USA.
Barton
K
K
Leiden
J M
JM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D002678:Chimera; D004268:DNA-Binding Proteins; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D011506:Proteins / Q000502:physiology; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D017384:Sequence Deletion; D013154:Spleen / Q000166:cytology; D013234:Stem Cells; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2