The mouse AIRE gene: Comparative genomic sequencing, gene organization, and expression

Mutations in the human AIRE gene (hAIRE) result in the development of an au toimmune disease named APECED (autoimmune polyendocrinopathy candidiasis ec todermal dystrophy; OMIM 240300). Previously, we have cloned hAIRE and show n that it codes for a putative transcription-associated Factor. Here we rep ort the cloning and characterization of Aire, the murine ortholog of hAIRE. Comparative genomic sequencing revealed that the structure of the AIRE gen e is highly conserved between human and mouse. The conceptual proteins shar e 73% homology and Feature the same typical Functional domains in both spec ies. RT-PCR analysis detected three splice variant isoforms in various mous e tissues, and interestingly one isoform was conserved in human, suggesting potential biological relevance of this product. In situ hybridization on m ouse and human histological sections showed that AIRE expression pattern wa s mainly restricted to a few cells in the thymus, calling for a tissue-spec ific function of the gene product.