Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/66002
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Type: Journal article
Title: Aire-Deficient C57BL/6 Mice Mimicking the Common Human 13-Base Pair Deletion Mutation Present with Only a Mild Autoimmune Phenotype
Author: Hubert, F.
Kinkel, S.
Crewther, P.
Cannon, P.
Webster, K.
Link, M.
Uibo, R.
O'Bryan, M.
Meager, A.
Forehan, S.
Smyth, G.
Mittaz, L.
Antonarakis, S.
Peterson, P.
Heath, W.
Scott, H.
Citation: Journal of Immunology, 2009; 182(6):3902-3918
Publisher: Amer Assoc Immunologists
Issue Date: 2009
ISSN: 0022-1767
1550-6606
Statement of
Responsibility: 
François-Xavier Hubert, Sarah A. Kinkel, Pauline E. Crewther, Ping Z. F. Cannon, Kylie E. Webster, Maire Link, Raivo Uibo, Moira K. O'Bryan, Anthony Meager, Simon P. Forehan, Gordon K. Smyth, Lauréane Mittaz, Stylianos E. Antonarakis, Pärt Peterson, William R. Heath, and Hamish S. Scott
Abstract: Autoimmune regulator (AIRE) is an important transcription regulator that mediates a role in central tolerance via promoting the "promiscuous" expression of tissue-specific Ags in the thymus. Although several mouse models of Aire deficiency have been described, none has analyzed the phenotype induced by a mutation that emulates the common 13-bp deletion in human APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) by disrupting the first plant homeodomain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, although symptoms were mild and the quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed its own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systemic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED.
Keywords: Thymus Gland; Cell Line; Animals; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Humans; Mice; Polyendocrinopathies, Autoimmune; Disease Models, Animal; Transcription Factors; Mutagenesis, Site-Directed; Molecular Mimicry; Amino Acid Sequence; Base Sequence; Base Pairing; Sequence Homology, Amino Acid; Phenotype; Molecular Sequence Data; Male
Rights: Copyright © 2009 by The American Association of Immunologists, Inc.
RMID: 0020111504
DOI: 10.4049/jimmunol.0802124
Grant ID: http://purl.org/au-research/grants/nhmrc/257501
http://purl.org/au-research/grants/nhmrc/264573
http://purl.org/au-research/grants/nhmrc/406700
Published version: http://www.jimmunol.org/content/182/6/3902.full
Appears in Collections:Microbiology and Immunology publications

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