Abstract
The transcription activator c-Myb is expressed at high levels in immature thymocytes and during T-cell activation and may be a regulator of T-cell differentiation. To investigate the role of c-Myb in T-cell development, we generated transgenic mice in which two dominant interfering Myb alleles, one a competitive inhibitor of DNA binding, and the other, an active repressor comprising the Myb DNA-binding domain linked to the Drosophila Engrailed transcription repressor domain, were expressed from early times onward in T cells. Both alleles partially blocked thymopoiesis and inhibited proliferation of mature T cells. The Myb-En chimera was the more efficient repressor and might serve as an archetype for the manufacture of other dominant interfering transcription factor alleles.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles*
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Animals
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Base Sequence
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Cell Differentiation
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Cell Division
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Drosophila
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Drosophila Proteins
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Gene Expression Regulation, Developmental / physiology*
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Genes, Dominant / physiology
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Homeodomain Proteins*
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Insect Hormones / genetics
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Lymphocyte Activation
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-myb
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Recombinant Fusion Proteins / physiology
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Repressor Proteins
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Sequence Deletion / physiology
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Spleen / cytology
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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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Transcription Factors / genetics
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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Drosophila Proteins
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En protein, Drosophila
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Homeodomain Proteins
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Insect Hormones
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-myb
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Recombinant Fusion Proteins
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Repressor Proteins
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Transcription Factors