Defect in rearrangement of the most 5' TCR-J alpha following targeted deletion of T early alpha (TEA): Implications for TCR alpha locus accessibility

Defect in rearrangement of the most 5' TCR-J alpha following targeted deletion of T early alpha (TEA): Implications for TCR alpha locus accessibility
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DOI:
10.1016/s1074-7613(00)80259-9
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发表时间:
1996-10-01
期刊:
影响因子:
32.4
通讯作者:
deVillartay, JP
deVillartay, JP
中科院分区:
医学1区
文献类型:
--
作者:
Villey, I;Caillol, D;deVillartay, JP

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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 removed by homologous recombination. Normal development of T alpha beta cells and the expression of other TCR alpha germline transcripts in TEA(-/-) mice ruled out an exclusive role for TEA in the overall accessibility 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 that TEA may control the DNA accessibility of a particular J alpha window. Moreover, the relative usage of every J alpha segment was affected. These results are consistent with TEA acting as a ''rearrangement-focusing'' element, targeting the primary waves of V alpha-J alpha recombination to the most 5' J alpha s in an ongoing TCR-J alpha rearrangement model.