DEFECT IN REARRANGEMENT OF THE MOST 5'-TCR-J-ALPHA FOLLOWING TARGETEDDELETION OF T-EARLY-ALPHA (TEA) - IMPLICATIONS FOR TCR-ALPHA LOCUS ACCESSIBILITY

To address the role of the TEA germline transcription, which initiates upstream of the TCR-J alpha s, in the regulation of TCR-J alpha locus accessibility, we created a mouse in which this region has been remov ed by homologous recombination. Normal development of T alpha beta cel ls and the expression of other TCR alpha germline transcripts in TEA(- /-) mice ruled out an exclusive role for TEA in the overall accessibil ity of the J alpha cluster. However, the rearrangement of the most 5' J alpha (J alpha 61 to J alpha 53) was severely impaired, indicating t hat TEA may control the DNA accessibility of a particular J alpha wind ow. Moreover, the relative usage of every J alpha segment was affected . These results are consistent with TEA acting as a ''rearrangement-fo cusing'' element, targeting the primary waves of V alpha-J alpha recom bination to the most 5' J alpha s in an ongoing TCR-J alpha rearrangem ent model.