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Fish SM , Bosma MJ
Abnormal Deletions in the T-Cell Receptor-6 Locus of Mouse Thymocytes
Molecular and Cellular Biology. 1994 Jul;14(7) :4455-4464
PMID: ISI:A1994NT62600014   
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Separate genetic elements (V, D, and J) encode the variable regions of lymphocyte antigen receptors. During early lymphocyte differentiation, these elements rearrange to form contiguous coding segments (VJ and VDJ) for a diverse array of variable regions. Rearrangement is mediated by a recombinase that recognizes short DNA sequences (signals) flanking V, D, and J elements. Signals flank both the 5' and 3' sides of each D element, thereby allowing assembly of a functional VDJ gene. However, in rearrangements involving the D delta 2 and J delta 1 elements of the mouse T-cell receptor delta (TCR delta) locus, we unexpectedly found that the D delta 2 element and a portion of its 5' signal are often deleted. Approximately 50% of recovered D delta 2 to J delta 1 rearrangements from thymocytes of adult wild-type mice showed such deletions. An additional 20% of the rearrangements contained standard D delta 2-J delta 1 coding junctions but showed some loss of nucleotides from the 5' D delta 2 signal. This loss was clearly associated with another event involving a site-specific cleavage at the 5' signal/coding border of D delta 2 and rejoining of the modified signal and coding ends. The abnormal loss of D delta 2 and a portion of the 5' D delta 2 signal was infrequently observed in D delta 2-to-J delta 1 rearrangements recovered from neonatal mice. The possible basis and significance of this age-dependent phenomenon are discussed.
English Article NT626 MOL CELL BIOL