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Title 

The T-Cell receptor ß variable gene promoter is required for efficient Vß rearrangement but not allelic exclusion

Authors 

Chun Jeih RyuB B HainesH R LeeYun Hee KangD D DraganovM H LeeC E WhitehurstHyo Jeong HongJ Chen

Publisher 

American Society for Microbiology

Issue Date 

2004

Citation 

Molecular and Cellular Biology, vol. 24, no. 16, pp. 7015-7023

Keywords 

allelesanimalsgene expression regulationgene rearrangement, beta-chain t-cell antigen receptorgenes, t-cell receptor betamicemice, knockoutmutationpromoter regions, genetictranscription, genetic

Abstract 

To investigate the role of promoters in regulating variable gene rearrangement and allelic exclusion, we constructed mutant mice in which a 1.2-kb region of the V beta 13 promoter was either deleted (P13(-/-)) or replaced with the simian virus 40 minimal promoter plus five copies of Gal4 DNA sequences (P13(R/R)). In P13(-/-) mice, cleavage, rearrangement, and transcription of V beta 13, but not the flanking V beta gene segments, were significantly inhibited. In P13(R/R) mice, inhibition of V beta 13 rearrangement was less severe and was not associated with any apparent reduction in V beta 13 cleavage. Expression of a T-cell receptor (TCR) transgene blocked cleavages at the normal V beta 13-recombination signal sequence junction and V beta 13 coding joint formation of both wild-type and mutant V beta 13 alleles. However, a low level of aberrant V beta 13 cleavage was consistently detected, especially in TCR transgenic P13(R/R) mice. These findings suggest that the variable gene promoter is required for promoting local recombination accessibility of the associated V beta gene segment. Although the promoter is dispensable for allelic exclusion, it appears to suppress aberrant V beta cleavages during allelic exclusion.

ISSN 

0270-7306

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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