Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / physiology
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CD3 Complex / biosynthesis
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CD4 Antigens / biosynthesis
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CD8 Antigens / biosynthesis
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Cell Division / physiology
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Cell Line
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Cell Survival / physiology*
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Chimera
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DNA-Binding Proteins*
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Lymphocyte Activation / physiology*
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Mice
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Proteins / physiology
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Proto-Oncogene Mas
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-ets
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Sequence Deletion
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Spleen / cytology
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Stem Cells
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T-Lymphocytes / immunology
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T-Lymphocytes / physiology*
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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CD3 Complex
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CD4 Antigens
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CD8 Antigens
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DNA-Binding Proteins
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ETS1 protein, human
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Ets1 protein, mouse
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MAS1 protein, human
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Proteins
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Proto-Oncogene Mas
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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Transcription Factors
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V(D)J recombination activating protein 2