1. Developmental regulation of TCR delta locus accessibility and expression by the TCR delta enhancer
- Author
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R J, Monroe, B P, Sleckman, B C, Monroe, B, Khor, S, Claypool, R, Ferrini, L, Davidson, and F W, Alt
- Subjects
Recombination, Genetic ,Mice ,Receptors, Antigen, T-Cell, alpha-beta ,T-Lymphocytes ,Gene Rearrangement, delta-Chain T-Cell Antigen Receptor ,Animals ,Gene Deletion ,Mice, Mutant Strains ,Genes, T-Cell Receptor delta ,Transcription Factors - Abstract
We have used gene-targeted mutation to assess the role of the T cell receptor delta (TCR delta) enhancer (E delta) in alphabeta and gammadelta T cell development. Mice lacking E delta exhibited no defects in alphabeta T cell development but had a severe reduction in thymic and peripheral gammadelta T cells and decreased VDJ delta rearrangements. Simultaneous deletion of both E delta and the TCR alpha enhancer (E alpha) demonstrated that residual TCR delta rearrangements were not driven by E alpha, implicating additional elements in TCR delta locus accessibility. Surprisingly, while deletion of E delta severely impaired germline TCR delta expression in double-negative thymocytes, absence of E delta did not affect expression of mature delta transcripts in gammadelta T cells. We conclude that E delta has an important role in TCR delta locus regulation at early, but not late, stages of gammadelta T cell development.
- Published
- 1999