Abstract
Notch proteins influence cell-fate decisions in many developing systems. Several gain-of-function studies have suggested a critical role for Notch 1 signaling in CD4-CD8 lineage commitment, maturation and survival in the thymus. However, we show here that tissue-specific inactivation of the gene encoding Notch 1 in immature (CD25+CD44-)T cell precursors does not affect subsequent thymocyte development. Neither steady-state numbers nor the rate of production of CD4+ and CD8+ mature thymocytes is perturbed in the absence of Notch 1. In addition, Notch 1-deficient thymocytes are normally sensitive to spontaneous or glucocorticoid-induced apoptosis. In contrast to earlier reports, these data formally exclude an essential role for Notch 1 in CD4-CD8 lineage commitment, maturation or survival.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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CD4 Antigens / genetics
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology*
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Cell Division
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Cell Lineage
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Cells, Cultured
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Gene Deletion
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Gene Targeting
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Glucocorticoids / pharmacology
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Integrases / genetics
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptor, Notch1
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Receptors, Cell Surface*
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Spleen / immunology
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T-Lymphocyte Subsets / classification
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Thymus Gland / cytology
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Thymus Gland / immunology*
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Transcription Factors*
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Transgenes
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Viral Proteins*
Substances
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CD4 Antigens
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Glucocorticoids
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Membrane Proteins
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Notch1 protein, mouse
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Receptor, Notch1
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Receptors, Cell Surface
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Transcription Factors
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Viral Proteins
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Cre recombinase
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Integrases