Aire deficient mice develop multiple features of APECED phenotype and show altered immune response
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 a...
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| Veröffentlicht in: | Human molecular genetics 2002-02, Vol.11 (4), p.397-409 |
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| container_title | Human molecular genetics |
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| creator | Ramsey, Chris Winqvist, Ola Puhakka, Lea Halonen, Maria Moro, Aune Kämpe, Olle Eskelin, Petra Pelto-Huikko, Markku Peltonen, Leena |
| description | 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-Vbeta 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. |
| doi_str_mv | 10.1093/hmg/11.4.397 |
| format | Article |
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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-Vbeta 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.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/11.4.397</identifier><identifier>PMID: 11854172</identifier><identifier>CODEN: HNGEE5</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Aire gene ; AIRE Protein ; Animals ; Autoantibodies - blood ; Autoantibodies - immunology ; Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ; CD4-CD8 Ratio ; Disease Models, Animal ; Gene Targeting ; Infertility - genetics ; Mice ; Mice, Knockout ; Polyendocrinopathies, Autoimmune - genetics ; Polyendocrinopathies, Autoimmune - immunology ; Polyendocrinopathies, Autoimmune - pathology ; T-Lymphocytes - immunology ; T-Lymphocytes - physiology ; Transcription Factors - genetics ; Transcription Factors - immunology ; Transcription Factors - physiology</subject><ispartof>Human molecular genetics, 2002-02, Vol.11 (4), p.397-409</ispartof><rights>Copyright Oxford University Press(England) Feb 15, 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11854172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramsey, Chris</creatorcontrib><creatorcontrib>Winqvist, Ola</creatorcontrib><creatorcontrib>Puhakka, Lea</creatorcontrib><creatorcontrib>Halonen, Maria</creatorcontrib><creatorcontrib>Moro, Aune</creatorcontrib><creatorcontrib>Kämpe, Olle</creatorcontrib><creatorcontrib>Eskelin, Petra</creatorcontrib><creatorcontrib>Pelto-Huikko, Markku</creatorcontrib><creatorcontrib>Peltonen, Leena</creatorcontrib><title>Aire deficient mice develop multiple features of APECED phenotype and show altered immune response</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>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-Vbeta 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.</description><subject>Aire gene</subject><subject>AIRE Protein</subject><subject>Animals</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - immunology</subject><subject>Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy</subject><subject>CD4-CD8 Ratio</subject><subject>Disease Models, Animal</subject><subject>Gene Targeting</subject><subject>Infertility - genetics</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Polyendocrinopathies, Autoimmune - genetics</subject><subject>Polyendocrinopathies, Autoimmune - immunology</subject><subject>Polyendocrinopathies, Autoimmune - pathology</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - physiology</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - immunology</subject><subject>Transcription Factors - physiology</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0DtPwzAUBWALgWgpbMzIYmBLazuOH2NVykOqBAPMkRNf01RxHOIE1H9PEGVhYbo60qcrnYPQJSVzSnS62Pq3BaVzPk-1PEJTygVJGFHpMZoSLXgiNBETdBbjjhAqeCpP0YRSlXEq2RQVy6oDbMFVZQVNj31VfscPqEOL_VD3VVsDdmD6oYOIg8PL5_VqfYvbLTSh37eATWNx3IZPbOoeOrC48n5oAI--DU2Ec3TiTB3h4nBn6PVu_bJ6SDZP94-r5SZpqZZ9YpQC66TkXGXSOVbo0mbOSE5KZ1ShZFkWGdDCMsuE4mwMqaBGG51aJsdiM3Tz87ftwvsAsc99FUuoa9NAGGIux2mYYvpfSFVKFJFshNd_4C4MXTOWyBmljGmh1IiuDmgoPNi87Spvun3-u3H6BZr8fdA</recordid><startdate>20020215</startdate><enddate>20020215</enddate><creator>Ramsey, Chris</creator><creator>Winqvist, Ola</creator><creator>Puhakka, Lea</creator><creator>Halonen, Maria</creator><creator>Moro, Aune</creator><creator>Kämpe, Olle</creator><creator>Eskelin, Petra</creator><creator>Pelto-Huikko, Markku</creator><creator>Peltonen, Leena</creator><general>Oxford Publishing Limited (England)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020215</creationdate><title>Aire deficient mice develop multiple features of APECED phenotype and show altered immune response</title><author>Ramsey, Chris ; Winqvist, Ola ; Puhakka, Lea ; Halonen, Maria ; Moro, Aune ; Kämpe, Olle ; Eskelin, Petra ; Pelto-Huikko, Markku ; Peltonen, Leena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p197t-a88edf7744857ff2b9cd5fa740cfa8b87ccb5e1bd2d26842b5e361a9a93d27643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Aire gene</topic><topic>AIRE Protein</topic><topic>Animals</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - immunology</topic><topic>Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy</topic><topic>CD4-CD8 Ratio</topic><topic>Disease Models, Animal</topic><topic>Gene Targeting</topic><topic>Infertility - genetics</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Polyendocrinopathies, Autoimmune - genetics</topic><topic>Polyendocrinopathies, Autoimmune - immunology</topic><topic>Polyendocrinopathies, Autoimmune - pathology</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - physiology</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - immunology</topic><topic>Transcription Factors - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ramsey, Chris</creatorcontrib><creatorcontrib>Winqvist, Ola</creatorcontrib><creatorcontrib>Puhakka, Lea</creatorcontrib><creatorcontrib>Halonen, Maria</creatorcontrib><creatorcontrib>Moro, Aune</creatorcontrib><creatorcontrib>Kämpe, Olle</creatorcontrib><creatorcontrib>Eskelin, Petra</creatorcontrib><creatorcontrib>Pelto-Huikko, Markku</creatorcontrib><creatorcontrib>Peltonen, Leena</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramsey, Chris</au><au>Winqvist, Ola</au><au>Puhakka, Lea</au><au>Halonen, Maria</au><au>Moro, Aune</au><au>Kämpe, Olle</au><au>Eskelin, Petra</au><au>Pelto-Huikko, Markku</au><au>Peltonen, Leena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aire deficient mice develop multiple features of APECED phenotype and show altered immune response</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2002-02-15</date><risdate>2002</risdate><volume>11</volume><issue>4</issue><spage>397</spage><epage>409</epage><pages>397-409</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><coden>HNGEE5</coden><abstract>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-Vbeta 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.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>11854172</pmid><doi>10.1093/hmg/11.4.397</doi><tpages>13</tpages></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Aire gene AIRE Protein Animals Autoantibodies - blood Autoantibodies - immunology Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy CD4-CD8 Ratio Disease Models, Animal Gene Targeting Infertility - genetics Mice Mice, Knockout Polyendocrinopathies, Autoimmune - genetics Polyendocrinopathies, Autoimmune - immunology Polyendocrinopathies, Autoimmune - pathology T-Lymphocytes - immunology T-Lymphocytes - physiology Transcription Factors - genetics Transcription Factors - immunology Transcription Factors - physiology |
| title | Aire deficient mice develop multiple features of APECED phenotype and show altered immune response |
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