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Early TCR expression and aberrant T cell development in mice with endogenous prerearranged T cell receptor genes.

The factors that regulate the rate of production of T cells by the thymus remain incompletely defined. To test whether generation of functional T cell receptors limits the rate of thymic T cell export, we made use of a line of mice, LN3alphabeta, that have endogenously prerearranged TCR genes. The prerearranged TCR genes were expressed abnormally early in hemopoietic development, indicating that RAG-mediated recombination, rather than transcription factor expression, is the key determinant of the initiation of robust TCR transcription. Thymic T cell export rates were similar between wild-type (wt) and LN3alphabeta mice, indicating that T cell maturation rates in these mice are determined by factors other than TCR gene rearrangement. In competitive bone marrow chimeras, however, LN3alphabeta thymocytes were out-competed by wt cells and failed to develop beyond the double-negative 4 stage. Furthermore, wt progenitors transplanted intrathymically into LN3alphabeta mice proliferated excessively, suggesting that increased proliferative signals in the LN3alphabeta thymus compensate for faulty T cell development driven by early TCR expression.

Pubmed ID: 17617584 RIS Download

Mesh terms: Animals | Cell Differentiation | Flow Cytometry | Gene Rearrangement, T-Lymphocyte | Genes, RAG-1 | Mice | Mice, Mutant Strains | Nuclear Transfer Techniques | Receptors, Antigen, T-Cell | Reverse Transcriptase Polymerase Chain Reaction | T-Lymphocytes | Thymus Gland

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Associated grants

  • Agency: NCI NIH HHS, Id: R01-CA87869
  • Agency: NCI NIH HHS, Id: R37-CA84198
  • Agency: NIAID NIH HHS, Id: R01-AI047457
  • Agency: NIAID NIH HHS, Id: T32 AI007290
  • Agency: NCI NIH HHS, Id: T32 CA009151
  • Agency: NICHD NIH HHS, Id: R01-HD0445022
  • Agency: NIAID NIH HHS, Id: 1F 32 AI 58521
  • Agency: NIAID NIH HHS, Id: R01-AI047458

Mouse Genome Informatics (Data, Gene Annotation)

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