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since 01/2001:

autoimmune regulator OKDB#: 2576
 Symbols: AIRE Species: human
 Synonyms: APS1, APSI, PGA1, AIRE1, APECED  Locus: 21q22.3 in Homo sapiens

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DNA Microarrays
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General Comment NCBI Summary: This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]
General function DNA binding, Transcription factor
Cellular localization Cytoplasmic, Nuclear
Ovarian function Oocyte maturation, Early embryo development
Comment Age-related differences in the translational landscape of mammalian oocytes. Del Llano E et al. (2020) Increasing maternal age in mammals is associated with poorer oocyte quality, involving higher aneuploidy rates and decreased developmental competence. Prior to resumption of meiosis, fully developed mammalian oocytes become transcriptionally silent until the onset of zygotic genome activation. Therefore, meiotic progression and early embryogenesis are driven largely by translational utilization of previously synthesized mRNAs. We report that genome-wide translatome profiling reveals considerable numbers of transcripts that are differentially translated in oocytes obtained from aged compared to young females. Additionally, we show that a number of aberrantly translated mRNAs in oocytes from aged females are associated with cell cycle. Indeed, we demonstrate that four specific maternal age-related transcripts (Sgk1, Castor1, Aire and Eg5) with differential translation rates encode factors that are associated with the newly forming meiotic spindle. Moreover, we report substantial defects in chromosome alignment and cytokinesis in the oocytes of young females, in which candidate CASTOR1 and SGK1 protein levels or activity are experimentally altered. Our findings indicate that improper translation of specific proteins at the onset of meiosis contributes to increased chromosome segregation problems associated with female ageing.////////////////// Aire promotes the self-renewal of embryonic stem cells through Lin28. Gu B et al. Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem(ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells. We presented the first evidence that the let-7 microRNA family contributed to the self-renewal promoting effect of Aire in ES cells. Moreover, we showed that Aire and Lin28 are co-expressed in the genital ridge, oocytes and cleavage stage embryos, and the expression level of Lin28 is correlated with expression level of Aire. Although it is widely considered to be a promiscuous gene expression activator, these results indicated that Aire promotes the self-renewal of embryonic stem cells through a specific pathway (i.e., the activation of Lin28 and inhibition of the let-7 microRNA family). The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. This study presents the first molecular pathway that incorporates Aire into the pluripotency network. Moreover, it presents the first evidence that microRNAs contributed to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. These functions reveal novel perspectives for studying the molecular mechanisms of pluripotent identity establishment and sustenance.
Expression regulated by
Ovarian localization Oocyte
Comment This gene is expressed at high levels in the oocyte based on the SymAltlas (
Follicle stages
Comment Expression and alternative splicing of the mouse autoimmune regulator gene (Aire) Ruan QG, et al . AIRE, the gene responsible for the autoimmune polyglandular syndrome type 1 (APS1) or APECED, may act as a transcription factor according to its predicated protein structure. Here we demonstrate the low expression level of the mouse Aire gene as it is undetectable by Northern blot analyses. However, RT-PCR analyses revealed expression of Aire in mouse thymus, ovary, lung, testis, kidney and adrenal gland. Barely detectable level of RT-PCR product was also found in thyroid gland and heart but no amplification was detected in pancreas, spleen and liver. Competitive RT-PCR assays demonstrated highest expression level of Aire mRNA in thymus. In addition to the complete cDNA (Aire or Aire-1a), we identified 11 alternative splicing forms (designated as Aire-1b, Aire-1c, Aire-1d, Aire-2a, Aire-2b, Aire-2c, Aire-2d, Aire-3a, Aire-3b, Aire-3c and Aire-3d). These forms result from combinations of four alternative splicing units (exon 10, exon 11, 12 bp in exon 6 and 3 bp in exon 8). The relative abundance of these splicing forms was also determined.
Phenotypes POF (premature ovarian failure)
Mutations 3 mutations

Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: The Autoimmune Regulator Prevents Premature Reproductive Senescence in Female Mice. Jasti S et al. Loss of function mutations in the autoimmune regulator (AIRE) gene are responsible for autoimmune polyglandular syndrome type 1 (APS-1), which commonly manifests as infertility in women. AIRE is a transcriptional regulator that promotes expression of tissue restricted antigens in the thymus, including antigens specific to the ovary. Thymic expression of ovarian genes under AIRE's control may be critical for preventing ovarian autoimmune disease. Because mice lacking Aire are an important APS-1 model, we examined the reproductive properties of female Aire-deficient mice (Aire(-/-)). Female Aire(-/-) mice on the BALB/c background were examined for reproductive parameters, including fertility, litter sizes, and ovarian follicular reserves. Although delayed puberty was observed in Aire(-/-) mice, all mice entered puberty and exhibited mating behavior. Only 50% of Aire(-/-) females gave an initial litter and only 16% were able to produce two litters. Ovarian histopathologic examination revealed that 83% of previously bred females lost all ovarian follicular reserves. Among virgin females, follicular depletion was observed in 25% by 8 wk, and by 20 wk, 50-60% of mice lost all follicles. This was associated with elevated serum follicle stimulating hormone and ovarian infiltration of proliferating CD3+ T lymphocytes. Ovulation rates of 6-wk-old Aire-deficient mice were reduced by 22%, but this difference was not statistically significant. Finally, transplantation experiments revealed that follicular loss depended on ovary-extrinsic factors. These results suggest that immune-mediated ovarian follicular depletion is a mechanism of infertility in Aire-deficient mice. The results have important implications in the pathogenesis of ovarian autoimmune disease in women.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Maclaren N, et al discussed autoimmune hypogonadism as part of an autoimmune polyglandular syndrome. The most compelling case for autoimmune mediated hypogonadism occurs when ovarian failure is part of an autoimmune polyglandular syndrome (APS). In patients with the rare, recessively inherited type 1 APS (APS-1), characterized by the triad of chronic mucocutaneous moniliasis, hypoparathyroidism, and Addison's disease, primary amenorrhea (elevated pituitary gonadotropins) or oligomenorrhea and infertility are constant features. Ovarian failure is associated with autoantibodies to steroid hormone secreting cells in the adrenal cortex, Leydig cells of the testes, granulosa/thecal cells of the Graffian follicles, corpus luteum, and the syncytiotrophoblast of the placenta. These autoantibodies react with 3 P450 enzymes involved with steroidogenesis, namely, 21-hydroxylase (adrenal specific), 17 alpha-hydroxylase, and the side chain cleavage enzyme. Recently the 14 exon, APS-1 (autoimmune regulator or AIRE) gene has been cloned (chr. 21p22.3), and multiple mutants discovered. Parents who are obligatory heterozygotes for a single mutant gene lack clinical features of APS-1. They also do not develop APS-1 autoantibodies. Thus, hypogonadal patients without features of APS-1 are unlikely to have AIRE gene mutations. In the more common APS-2/3, characterized by combinations of autoimmune thyroid disease, immune mediated type 1 diabetes, vitiligo, pernicious anemia, and Addison's disease (type 2, not type 3), ovarian disease may be seen. In primary hypogonadism outside of the context of an APS, these autoantibodies are rare.

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) and in their relatives. Cervato S et al. (2009) Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is a rare syndrome characterized by chronic candidiasis, chronic hypoparathyroidism and Addison's disease. APECED has been associated with mutations in autoimmune regulator (AIRE) gene. Our aim is to perform a genetic analysis of the AIRE gene in Italian APECED patients and in their relatives. Design AIRE mutations were determined by DNA sequencing in all subjects. Patients were tested for clinical autoimmune or non-autoimmune diseases, or for organ and non-organ specific autoantibodies. A total of 24 Italian patients with APECED (15 from the Venetian region, 2 from Southern-Tyrol, 4 from Apulia, 3 from Sicily), 25 relatives and 116 controls were studied. Ten out of the 15 Venetian patients (66%) were homozygous for R257X or compound heterozygous with 1094-1106del13. One patient was homozygous for 1094-1106del13 and another for R139X. A novel mutation (1032-1033delGT) in combination with 1094-1106del13 was identified in one patient. No mutations were found in two cases. Two patients from Southern Tyrol were homozygous for R257X and for 1094-1106del13bp. All patients from Apulia were homozygous or heterozygous for W78R combined with Q358X. The patients from Sicily were homozygous for R203X or compound heterozygous with R257X. The analysis of the genotype-phenotype revealed that patients carrying 1094-1106del13 at the onset of Addison's disease were significantly older than those carrying other mutations. The genetic study of 25 relatives identified 20 heterozygous subjects. They suffered from various autoimmune and non-autoimmune diseases but no major disease of APECED was found. These data demonstrate the great genetic heterogeneity for the AIRE mutations in Italian APECED patients, and that the heterozygosity for AIRE mutations do not produce APECED.//////////////////

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created: Aug. 2, 2004, 10:03 a.m. by: hsueh   email:
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last update: Sept. 23, 2020, 2:53 p.m. by: hsueh    email:

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