Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire.

The Journal of Clinical Investigation
Maureen A SuMark S Anderson

Abstract

Homozygous loss-of-function mutations in AIRE cause autoimmune polyglandular syndrome type 1 (APS 1), which manifests in a classic triad of hypoparathyroidism, adrenal insufficiency, and candidiasis. Interestingly, a kindred with a specific G228W AIRE variant presented with an autosomal dominant autoimmune phenotype distinct from APS 1. We utilized a novel G228W-knockin mouse model to show that this variant acted in a dominant-negative manner to cause a unique autoimmunity syndrome. In addition, the expression of a large number of Aire-regulated thymic antigens was partially inhibited in these animals, demonstrating the importance of quantitative changes in thymic antigen expression in determining organ-specific autoimmunity. Furthermore, the dominant-negative effect of the G228W variant was exerted through recruitment of WT Aire away from active sites of transcription in the nucleus of medullary thymic epithelial cells in vivo. Together, these results may demonstrate a mechanism by which autoimmune predisposition to phenotypes distinct from APS 1 can be mediated in a dominant-negative fashion by Aire.

References

Dec 17, 1997·Nature Genetics·K NagamineN Shimizu
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M B EisenD Botstein
Apr 20, 1999·Biochemical and Biophysical Research Communications·M HeinoK Krohn
Jun 28, 2001·Nature Structural Biology·M J BottomleyM Sattler
Sep 5, 2001·The Journal of Biological Chemistry·P G KumarJ X She
Sep 6, 2001·The Journal of Experimental Medicine·B SalomonJ A Bluestone
Jan 17, 2002·Journal of Immunological Methods·D H D GrayR L Boyd
Mar 4, 2003·Nature Immunology·Adrian ListonChristopher C Goodnow
Mar 5, 2003·European Journal of Immunology·Katsuichi MiyamotoTakashi Yamamura
Mar 18, 2003·The Journal of Clinical Investigation·Karine Thébault-BaumontChristian Boitard
Aug 19, 2003·Nature Reviews. Molecular Cell Biology·Angus I Lamond, David L Spector
Jan 22, 2004·The Journal of Experimental Medicine·Daisuke UchidaMitsuru Matsumoto
Feb 20, 2004·Human Mutation·Maria HalonenPetra Eskelin
Apr 17, 2004·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·H-P TörökC Folwaczny
May 20, 2004·The Journal of Biological Chemistry·Hiroko AkiyoshiMitsuru Matsumoto
May 26, 2004·Clinics in Laboratory Medicine·Qing-Guo Ruan, Jin-Xiong She
Jun 1, 2004·Molecular Biology of the Cell·Noriko SaitohDavid L Spector
Oct 20, 2004·The Journal of Experimental Medicine·Adrian ListonChristopher C Goodnow
Jan 15, 2005·Biochemical and Biophysical Research Communications·Sharad PurohitJin-Xiong She
May 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jonathan B JohnnidisDiane J Mathis
Jun 29, 2005·The Journal of Experimental Medicine·Jens DerbinskiBruno Kyewski
Aug 23, 2005·Immunity·Mark S AndersonDiane Mathis
Sep 21, 2005·The Journal of Experimental Medicine·Wenyu JiangChristophe Benoist
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hélène Bour-JordanJeffrey A Bluestone
Apr 22, 2006·The Journal of Clinical Investigation·Shino NikiMitsuru Matsumoto
Nov 15, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·F FerreraF Indiveri
Nov 23, 2006·The Journal of Experimental Medicine·Jason DeVossMark S Anderson
Nov 30, 2006·Cell·David L Spector
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Geoffrey O GillardAndrew G Farr
Oct 3, 2007·The Journal of Experimental Medicine·Daniel GrayDiane Mathis

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Citations

Sep 10, 2010·Hepatology International·Ye H OoDavid H Adams
Nov 15, 2008·Nature Reviews. Immunology·Pärt PetersonAna Rebane
Sep 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Mireia Guerau-de-ArellanoChristophe Benoist
Oct 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Andrew S KohDiane Mathis
Jul 5, 2011·Nucleic Acids Research·Kristina ŽumerB Matija Peterlin
Mar 24, 2009·Annual Review of Immunology·Diane Mathis, Christophe Benoist
Feb 5, 2009·Pediatric Research·Maureen A Su, Mark S Anderson
Oct 10, 2008·The Journal of Clinical Endocrinology and Metabolism·Mark S Anderson
Jan 6, 2015·Molecular Therapy. Methods & Clinical Development·Brandon K SackDavid M Markusic
Jan 10, 2012·Annual Review of Immunology·Mickie H Cheng, Mark S Anderson
Feb 2, 2013·Cancer Research·Meng-Lei ZhuMaureen A Su
Oct 10, 2015·European Journal of Immunology·Jakub Abramson, Yael Goldfarb
Dec 18, 2010·Current Opinion in Immunology·Mark S Anderson, Maureen A Su
Oct 17, 2009·Current Opinion in Immunology·James M GardnerShannon J Turley
Mar 31, 2009·Endocrinology and Metabolism Clinics of North America·Noriko ShikamaGeorg A Holländer
Apr 23, 2009·Journal of Internal Medicine·G A Holländer, P Peterson
Dec 17, 2008·Annals of the New York Academy of Sciences·Lars-Oliver TykocinskiBruno Kyewski
Jan 13, 2012·Annals of the New York Academy of Sciences·Kai Kisand, Pärt Peterson
Apr 15, 2011·Immunological Reviews·Todd C Metzger, Mark S Anderson
Apr 10, 2014·Immunological Reviews·Peter A SavageSven Malchow
Mar 22, 2016·The Journal of Clinical Investigation·Pearl Bakhru, Maureen A Su
Nov 4, 2015·The Journal of Experimental Medicine·Taylor N LaFlamMark S Anderson
Mar 15, 2016·Nature Reviews. Immunology·Mark S Anderson, Maureen A Su
Apr 26, 2015·Journal of Autoimmunity·Iñaki AlvarezDolores Jaraquemada
Jul 5, 2015·Journal of Clinical Immunology·Kai Kisand, Pärt Peterson
Apr 19, 2016·Immunological Reviews·Jakub Abramson, Eystein S Husebye
Nov 28, 2013·Biochimica Et Biophysica Acta·Roberto Perniola, Giovanna Musco
Jul 16, 2013·Journal of Autoimmunity·Hélène Bour-JordanJeffrey A Bluestone
Apr 24, 2010·Immunity·Eystein S Husebye, Mark S Anderson
Jan 21, 2010·Cell·Jakub AbramsonDiane Mathis
Aug 10, 2016·Current Opinion in Immunology·Øyvind BruserudEystein S Husebye
Dec 13, 2016·Nature Immunology·Yonatan HerzigJakub Abramson

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Methods Mentioned

BETA
flow cytometry
transgenic
confocal microscopy
immunoprecipitation
PCR
transfection
NMR
fluorescence microscopy
chip
chips

Software Mentioned

GraphPad
MetaMorph
Prism

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