Developmental regulation of TCR delta locus accessibility and expression by the TCR delta enhancer.
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.
Monroe
R J
RJ
Howard Hughes Medical Institute, Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sleckman
B P
BP
Monroe
B C
BC
Khor
B
B
Claypool
S
S
Ferrini
R
R
Davidson
L
L
Alt
F W
FW
D000818:Animals; D017353:Gene Deletion; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D019676:Genes, T-Cell Receptor delta / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology; D011995:Recombination, Genetic; D013601:T-Lymphocytes; D014157:Transcription Factors / Q000502:physiology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors