Abstract
Transgenic mice with human CD3epsilon gene have been shown to exhibit early arrest of T cell development in the thymus. The present study shows that, instead of T cells, B cells are generated in the thymus of a line, tg epsilon26, of the human CD3epsilon transgenic mice. The accumulation of mature B cells in the thymus was found only in tg epsilon26 mice, not in other human CD3epsilon transgenic mouse lines or other T cell-deficient mice, including CD3-epsilon knockout mice and TCR-beta/TCR-delta double knockout mice. Hanging drop-mediated transfer into 2-deoxyguanosine-treated thymus lobes showed that lymphoid progenitor cells rather than thymus stromal cells were responsible for abnormal B cell development in tg epsilon26 thymus, and that tg epsilon26 fetal liver cells were destined to become B cells in normal thymus even in the presence of normal progenitor cells undergoing T cell development. These results indicate that lymphoid progenitor cells in tg epsilon26 mice are genetically defective in thymic choice between T cells and B cells, generating B cells even in normal thymus environment. Interestingly, tg epsilon26 thymocytes expressed GATA-3 and TCF-1, but not LEF-1 and PEBP-2alpha, among T cell-specific transcription factors that are involved in early T cell development, indicating that GATA-3 and TCF-1 expressed during thymocyte development do not necessarily determine the cell fate into T cell lineage. Thus, tg epsilon26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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B-Lymphocytes / pathology*
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CD3 Complex*
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Cell Differentiation
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Cell Lineage / genetics*
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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GATA3 Transcription Factor
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Gene Expression Regulation, Developmental
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
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Hematopoiesis / genetics*
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Hepatocyte Nuclear Factor 1-alpha
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Humans
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Immunologic Deficiency Syndromes / immunology
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Immunologic Deficiency Syndromes / pathology*
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Liver / embryology
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Liver / pathology
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Lymphoid Enhancer-Binding Factor 1
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Mice
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Mice, Knockout
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Mice, Transgenic / genetics
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Mice, Transgenic / immunology*
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Organ Culture Techniques
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Polymerase Chain Reaction
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Receptors, Antigen, T-Cell / deficiency
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / physiology*
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Receptors, Antigen, T-Cell, alpha-beta / deficiency
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / deficiency
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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T Cell Transcription Factor 1
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Thymus Gland / pathology*
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Trans-Activators / biosynthesis
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Transcription Factor AP-2
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transgenes
Substances
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CD3 Complex
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CD3E protein, human
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DNA-Binding Proteins
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GATA3 Transcription Factor
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GATA3 protein, human
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Gata3 protein, mouse
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Hepatocyte Nuclear Factor 1-alpha
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Hnf1a protein, mouse
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LEF1 protein, human
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Lef1 protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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T Cell Transcription Factor 1
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TCF7 protein, human
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Trans-Activators
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Transcription Factor AP-2
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Transcription Factors