Abstract
The Id proteins are inhibitors of basic-Helix-Loop-Helix transcription factor function that have been implicated in the control of cell differentiation and proliferation. To study the role of Id proteins in the control of T cell development, we generated transgenic mice that overexpress the Id2 protein in thymocytes. We detect a significant expansion of the early CD4(-)CD8(+)TCR(-) thymocyte stage and a depletion of the thymocytes of the subsequent developmental stages. These data indicate that the overexpression of Id2 leads to a stage-specific developmental block early in thymopoiesis. In addition, progeny mice from five of the six Id2 transgenic founder lines succumb to aggressive T cell hyperproliferation that resembles lymphoma. Thus, overexpression of the Id2 protein has profound effects on T cell development and oncogenesis, consistent with the hypothesis that the bHLH proteins play critical roles in these processes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology*
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Female
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Helix-Loop-Helix Motifs / genetics
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Helix-Loop-Helix Motifs / immunology
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / immunology
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Inhibitor of Differentiation Protein 2
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Lymphocyte Activation / genetics
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Lymphoma, T-Cell / etiology
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Lymphoma, T-Cell / genetics
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Lymphoma, T-Cell / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Transgenic
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Repressor Proteins / genetics*
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Repressor Proteins / immunology*
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology*
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Thymus Gland / cytology
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Thymus Gland / immunology
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Transcription Factors*
Substances
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DNA-Binding Proteins
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Idb2 protein, mouse
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Inhibitor of Differentiation Protein 2
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Repressor Proteins
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Transcription Factors