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Defective activation and survival of T cells lacking the Ets-1 transcription factor

Abstract

THE Ets-1 proto-oncogene1 is a member of the Ets family of eukaryotic transcription factors2á¤-7. Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals4,5,8,9. Ets-1 is preferentially expressed at high levels in B and T cells of adult mice10,11 and is regulated during both thymocyte development11 and T-cell activation*12, 13. To study the role of Ets-1 in T-cell development and function we have used theRAG-2-/- complementation system14 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)-α/β. 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.

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Muthusamy, N., Barton, K. & Leiden, J. Defective activation and survival of T cells lacking the Ets-1 transcription factor. Nature 377, 639–642 (1995). https://doi.org/10.1038/377639a0

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