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Here, we used a combined genetic approach for risk\u2010loci identification in a prototypic, organ\u2010specific, autoimmune disease, namely experimental epidermolysis bullosa acquisita (<jats:styled-content style=\"fixed-case\">EBA<\/jats:styled-content>), in which autoantibodies to type <jats:styled-content style=\"fixed-case\">VII<\/jats:styled-content> collagen (<jats:styled-content style=\"fixed-case\">COL7<\/jats:styled-content>) and neutrophil activation cause mucocutaneous blisters. Anti\u2010<jats:styled-content style=\"fixed-case\">COL7 IgG<\/jats:styled-content> induced moderate blistering in most inbred mouse strains, while some showed severe disease or were completely protected. Using publicly available genotyping data, we identified haplotype blocks that control blistering and confirmed two haplotype blocks in outbred mice. To identify the blistering\u2010associated genes, haplotype blocks encoding genes that are differentially expressed in <jats:styled-content style=\"fixed-case\">EBA<\/jats:styled-content>\u2010affected skin were considered. This procedure identified nine genes, including <jats:italic>retinoid\u2010related orphan receptor alpha<\/jats:italic> (<jats:italic>ROR\u03b1<\/jats:italic>), known to be involved in neurological development and function. After anti\u2010<jats:styled-content style=\"fixed-case\">COL7 IgG<\/jats:styled-content> injection, <jats:styled-content style=\"fixed-case\">ROR\u03b1<\/jats:styled-content>+\/\u2212 mice showed reduced blistering and homozygous mice were completely resistant to <jats:styled-content style=\"fixed-case\">EBA<\/jats:styled-content> induction. Furthermore, pharmacological <jats:styled-content style=\"fixed-case\">ROR\u03b1<\/jats:styled-content> inhibition dose\u2010dependently blocked reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) release from activated neutrophils but did not affect migration or phagocytosis. Thus, forward genomics combined with multiple validation steps identifies <jats:styled-content style=\"fixed-case\">ROR\u03b1<\/jats:styled-content> to be essential to drive inflammation in experimental <jats:styled-content style=\"fixed-case\">EBA<\/jats:styled-content>. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4556","type":"journal-article","created":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T13:59:28Z","timestamp":1431007168000},"page":"111-122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The retinoid\u2010related orphan receptor alpha is essential for the end\u2010stage effector phase of experimental epidermolysis bullosa acquisita"],"prefix":"10.1002","volume":"237","author":[{"given":"Hengameh","family":"Sadeghi","sequence":"first","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yask","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of L\u00fcbeck  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