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Comment |
Halonen M et al 2001 reported the subcellular Location and Expression Pattern of Autoimmune Regulator (Aire), the Mouse Orthologue for Human Gene Defective in Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED).
They studied the expression of Aire in transfected cell lines and in adult mouse tissues. The results show that Aire has a dual subcellular location and that it is expressed in multiple immunologically relevant tissues such as the thymus, spleen, lymph nodes, and bone marrow. In addition, Aire expression was detected in various other tissues such as kidney, testis, adrenal glands, liver, and ovary. These findings suggest that APECED protein might also have a function(s) outside the immune system.
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Mutations |
2 mutations
Species: human
Mutation name: None
type: naturally occurring
fertility: unknown
Comment: Betterle et al. (1998) reviewed the clinical findings of APECED. They found that the spectrum of associated minor clinical diseases includes other autoimmune endocrinopathies (hypergonadotropic hypogonadism, insulin-dependent diabetes mellitus, autoimmune thyroid diseases, and pituitary defects), autoimmune or immuno-mediated gastrointestinal diseases (chronic atrophic gastritis, pernicious anemia, and malabsorption), chronic active hepatitis, autoimmune skin diseases (vitiligo and alopecia), ectodermal dystrophy, keratoconjunctivitis, immunologic defects (cellular and humoral), asplenia, and cholelithiasis. The first manifestations usually occur in childhood with the 3 main diseases developing in the first 20 years of life, and other accompanying diseases continue to appear until at least the fifth decade.
Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: Autoimmune Regulator (AIRE) is required in female mice for optimal embryonic development and implantation1. Warren BD et al. (2019) Autoimmune Regulator (AIRE) regulates central immune tolerance by inducing expression of tissue-restricted antigens in thymic medullary epithelial cells, thereby ensuring elimination of autoreactive T cells. Aire mutations in humans and targeted Aire deletion in mice results in multi-organ autoimmune disease, known in humans as Autoimmune Polyglandular Syndrome Type 1 (APS-1). APS-1 is characterized by presence of adrenal insufficiency, chronic mucosal candidiasis, and/or hypoparathyroidism. Additionally, females often present with gonadal insufficiency and infertility. Aire-deficiency (KO) in mice results in oophoritis and age-dependent depletion of follicular reserves. In this study, we found that while the majority of young 6-week-old Aire-KO females had normal follicular reserves, mating behavior, and ovulation rates, 50% of females experienced embryonic loss between gestation day (GD) 5.5 and 7.5 that could not be attributed to insufficient progesterone production or decidualization. The quality of GD0.5 embryos recovered from Aire KO mice was reduced, and when cultured in vitro, embryos displayed limited developmental capacity in comparison to those recovered from WT mice. Further, embryos flushed from Aire KO dams at GD3.5 were developmentally delayed in comparison to WT controls and had reduced trophoblastic outgrowth in vitro. We conclude that AIRE does not play a direct role in uterine decidualization. Rather, reduced fertility of Aire-deficient females is likely due to multiple factors, including oophoritis, delayed preimplantation development, and compromised implantation. These effects may be explained by autoimmune targeting of the ovary, embryo, or both. Alternatively, altered embryonic development could be due to a direct role for AIRE in early embryogenesis.//////////////////
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