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Publication : The Downstream Transcriptional Enhancer, Ed, positively regulates mouse Ig kappa gene expression and somatic hypermutation.

First Author  Xiang Y Year  2008
Journal  J Immunol Volume  180
Issue  10 Pages  6725-32
PubMed ID  18453592 Mgi Jnum  J:134885
Mgi Id  MGI:3790011 Doi  10.4049/jimmunol.180.10.6725
Citation  Xiang Y, et al. (2008) The Downstream Transcriptional Enhancer, Ed, positively regulates mouse Ig kappa gene expression and somatic hypermutation. J Immunol 180(10):6725-32
abstractText  The mouse Igkappa locus has three known transcriptional enhancers: the matrix association region/intronic enhancer, the 3' enhancer (E3'), and the further downstream enhancer (Ed). Previous studies have shown that both matrix association region/intronic and E3' enhancers are required for maximal gene rearrangement of the locus, and that E3' is also required for maximal expression and somatic hypermutation (SHM). To functionally elucidate Ed in vivo, we generated knockout mice with a targeted germline deletion of Ed. Ed deleted homozygous mice (Ed-/-) have moderately reduced numbers of Igkappa expressing B cells and correspondingly increased numbers of Iglambda expressing B cells in spleen. Ed-/- mice also have decreased Igkappa mRNA expression in resting and T cell-dependent activated splenic B cells and reduced Igkappa chains in sera. However, our analysis indicates that Igkappa gene rearrangement is normal in Ed-/- mice. In addition, our results show that Ed-/- mice exhibit reduced SHM in the Igkappa gene J-C intronic region in germinal center B cells from Peyer's patches. We conclude that Ed positively regulates Igkappa gene expression and SHM, but not gene rearrangement.
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