Isolation and characterization of the mouse Aire gene

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder characterized by Addison's disease and/ or hypoparathyroidism and/or chronic mucocutaneous candidiasis, Patients ma y also have other clinical symptoms both within and outside the endocrine s ystem, mainly as a result of autoimmunity against organ-specific autoantige ns. The gene for APECED has recently been identified and termed AIRE (for A utoimmune REgulator), APECED is a model of organ-specific autoimmunity and isolation and characterization of the homologous mouse gene, Aire, will pro vide tools for dissection of the mechanisms underlying this human disorder and defining molecular pathways involved in organ-specific autoimmunity. We have isolated and completely sequenced the mouse Aire gene which is split into 14 exons over 13 kb and encodes a predicted protein of 552 amino acids . The predicted mouse and human AIRE proteins are 71% identical and contain motifs suggestive of a transcriptional regulator. Additional conserved mot ifs are emerging in the AIRE/Aire proteins including a nuclear localization signal, an "ASS" domain, and a "SAND" domain. The human and mouse AIRE pro moters have conserved sites for several thymus-specific transcription facto rs and others important in hematopoesis, consistent with its expression in rare cells of the thymus medulla, lymph nodes, and fetal liver. We have map ped mouse Aire to mouse chromosome 10 by FISH, to the same region as Pwp2 a nd Pfkl, confirming synteny to the corresponding region of human chromosome 21. (C) 1999 Academic Press.