Human Molecular Genetics, 2002, Vol. 11, No. 4 397-409
© 2002 Oxford University Press
Aire deficient mice develop multiple features of APECED phenotype and show altered immune response
1Department of Human Genetics, UCLA School of Medicine, Gonda Center, University of California Los Angeles, Los Angeles, CA, USA, 2Department of Internal Medicine, University Hospital of Uppsala, Uppsala, Sweden, 3Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland, 4Hospital for Children and Adolescence, Helsinki University Hospital, Helsinki, Finland, 5Department of Developmental Biology and Pathology, Medical School, Tampere University and Tampere University Hospital, Tampere, Finland and 6Department of Medical Genetics, University of Helsinki, Helsinki, Finland
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autosomal recessive disease caused by mutations in the AIRE gene. Here we have produced knock-out mice for the Aire gene. The Aire–/– mice develop normally; however, autoimmune features of APECED in Aire–/– mice are evident, including multiorgan lymphocytic infiltration, circulating autoantibodies and infertility. The distribution of B and T cells and thymic maturation as well as activation of T cells appear normal, while the TCR-Vß repertoire is altered in peripheral T cells of Aire–/– mice. When mice are challenged with immunization, the peripheral T cells of Aire–/– mice have a 3–5-fold increased proliferation. These findings suggest that the Aire gene is not necessary for normal T cell education and development, while a defect in immune response detected in challenged Aire–/– mice underlines the crucial role of AIRE/Aire in maintaining homeostatic regulation in the immune system.
+ To whom correspondence should be addressed at: Department of Human Genetics, UCLA School of Medicine, Gonda Center, 695 Charles E. Young Drive South, Los Angeles, CA 90095-7088, USA. Tel: +1 310 794 5631; Fax: +1 310 794 5446; Email: lpeltonen@mednet.ucla.edu The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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