Abstract
Nuclear factor of activated T cells (NFAT) is a family of four related transcription factors implicated in cytokine and early response gene expression in activated lymphocytes. Here we report that NFAT4, in contrast to NFATp and NFATc, is preferentially expressed in DP thymocytes. Mice lacking NFAT4 have impaired development of CD4 and CD8 SP thymocytes and peripheral T cells as well as hyperactivation of peripheral T cells. The thymic defect is characterized by increased apoptosis of DP thymocytes. The increased apoptosis and hyperactivation may reflect heightened sensitivity to TcR-mediated signaling. Further, mice lacking NFAT4 have impaired production of Bcl-2 mRNA and protein. NFAT4 thus plays an important role in the successful generation and survival of 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 / genetics
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CD4-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / cytology
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Cell Differentiation / genetics
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Cell Survival / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / physiology*
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Gene Expression / drug effects
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Gene Targeting / methods
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Genes, bcl-2 / genetics
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HLA-DP Antigens / analysis
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / genetics
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Lymphocyte Count
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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NFATC Transcription Factors
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / physiology
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / physiology
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Spleen / cytology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / physiology
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology
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T-Lymphocytes / physiology
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Thymus Gland / cytology
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Thymus Gland / immunology
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Transcription Factors / biosynthesis
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Transcription Factors / physiology*
Substances
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DNA-Binding Proteins
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HLA-DP Antigens
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NFATC Transcription Factors
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Nfatc3 protein, mouse
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Nuclear Proteins
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Receptors, Antigen, T-Cell
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Transcription Factors