Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype

摘要: Autoimmune regulator (AIRE) is an important transcription that mediates a role in central tolerance via promoting the "promiscuous" expression of tissue-specific Ags thymus. Although several mouse models Aire deficiency have been described, none has analyzed phenotype induced by mutation emulates common 13-bp deletion human APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) disrupting first plant homeodomain exon 8. Aire-deficient mice with corresponding showed some disturbance medullary epithelial compartment, but at phenotypic level their T cell compartment appeared relatively normal thymus and periphery. An increase number activated cells was evident, autoantibodies against organs were detected. At histological level, lymphocytic infiltration indicated development autoimmunity, although symptoms mild quality life for equivalent to wild-type littermates, exception male infertility. Vbeta CDR3 length analysis suggested each developed its own polyclonal autoimmune repertoire. Finally, given prevalence candidiasis patients, we examined control infection Candida albicans mice. No disease susceptibility found either oral or systemic infection. These observations support view additional genetic and/or environmental factors contribute substantially overt nature autoimmunity associated mutations, even mutations identical those humans APECED.