Mechanistic dissection of dominant AIRE mutations in mouse models reveals evidence for AIRE auto-regulation [RNA-seq]
Using mouse models of several recessive and putative dominant-negative patient mutations we were able to dissect the mechanisms that underlie the recessive and dominant-negative capacities of the corresponding AIRE mutants, including a newly identified dominant-negative variant C446G We also identify an auto-regulatory mechanism by which AIRE negatively modulates its own expression. Overall design: mRNA profiles of mature medullary thymic epithelial cells (mTEChi) from young (4-7 weeks old) of all mutant mice generated in the study, as well as Aire-/-,were generated by deep sequencing, using the MARSseq method.