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Publication : Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination.

First Author  Misaghi S Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  39 Pages  15770-5
PubMed ID  24019479 Mgi Jnum  J:201147
Mgi Id  MGI:5511085 Doi  10.1073/pnas.1221661110
Citation  Misaghi S, et al. (2013) Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination. Proc Natl Acad Sci U S A 110(39):15770-5
abstractText  Preceding antibody constant regions are switch (S) regions varying in length and repeat density that are targets of activation-induced cytidine deaminase. We asked how participating S regions influence each other to orchestrate rearrangements at the IgH locus by engineering mice in which the weakest S region, Sepsilon, is replaced with prominent recombination hotspot Smu. These mice produce copious polyclonal IgE upon challenge, providing a platform to study IgE biology and therapeutic interventions. The insertion enhances epsilon germ-line transcript levels, shows a preference for direct vs. sequential switching, and reduces intraswitch recombination events at native Smu. These results suggest that the sufficiency of Smu to mediate IgH rearrangements may be influenced by context-dependent cues.
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