{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:07:15Z","timestamp":1791252435111,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2008,6,3]],"date-time":"2008-06-03T00:00:00Z","timestamp":1212451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Y\u2010linked autoimmune accelerating (<jats:italic>Yaa<\/jats:italic>) locus drives the transition to fatal lupus nephritis when combined with B6.<jats:italic>Sle1<\/jats:italic> in our C57BL\/6J (B6)\u2010congenic model of systemic autoimmunity. We and others recently demonstrated that the translocation of a cluster of X\u2010linked genes onto the Y\u2004chromosome is the genetic lesion underlying <jats:italic>Yaa<\/jats:italic> (Subramanian, S. <jats:italic>et al.<\/jats:italic>, <jats:italic>Proc. Natl. Acad. Sci. USA<\/jats:italic> 2006. 103: 9970\u20139975; Pisitkun, P. <jats:italic>et al.<\/jats:italic>, <jats:italic>Science<\/jats:italic> 2006. 312: 1669\u20131672). In male mice carrying <jats:italic>Yaa<\/jats:italic>, the transcription of several genes within the translocated segment is increased roughly twofold. Although the translocated X\u2004chromosome segment in <jats:italic>Yaa<\/jats:italic> may contain as many as 16\u2004genes, the major candidate gene for causation of the <jats:italic>Yaa\u2010<\/jats:italic>associated autoimmune phenotypes has been TLR7. To confirm the role of TLR7 in <jats:italic>Yaa<\/jats:italic>\u2010mediated autoimmune phenotypes, we introgressed a targeted disruption of TLR7 (TLR7<jats:sup>\u2013<\/jats:sup>) onto B6.<jats:italic>Sle1Yaa<\/jats:italic> to produce B6.<jats:italic>Sle1Yaa<\/jats:italic>TLR7<jats:sup>\u2013<\/jats:sup> and examined evidence of disease at 6 and 9\u2004months of age. Our results demonstrate that the up\u2010regulation of TLR7 in the B6.<jats:italic>Sle1Yaa<\/jats:italic> strain is responsible for splenomegaly, glomerular nephritis and the majority of the cellular abnormalities of B, T and myeloid cells. The up\u2010regulation of TLR7 was also responsible for driving the infiltration and activation of leukocytes in the kidney, in which activated T cells were a primary component. However, the resolution of TLR7 up\u2010regulation did not eliminate the enhanced humoral autoimmunity observed in B6.<jats:italic>SleYaa<\/jats:italic>, suggesting that additional elements in the translocation may contribute to the disease phenotype.<\/jats:p><jats:p>See accompanying commentary <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1002\/eji.200838478\">http:\/\/dx.doi.org\/10.1002\/eji.200838478<\/jats:ext-link><\/jats:p>","DOI":"10.1002\/eji.200838138","type":"journal-article","created":{"date-parts":[[2008,6,3]],"date-time":"2008-06-03T11:20:14Z","timestamp":1212492014000},"page":"1971-1978","source":"Crossref","is-referenced-by-count":172,"title":["<i>Yaa<\/i> autoimmune phenotypes are conferred by overexpression of TLR7"],"prefix":"10.1002","volume":"38","author":[{"given":"Anna\u2010Marie","family":"Fairhurst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010hee","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang\u2010Hong","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Boudreaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2004J.","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Casco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan\u2010Zhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u2004E.","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward\u2004K.","family":"Wakeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,6,25]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(06)92001-X"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00201-1"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90100-7"},{"key":"e_1_2_8_4_2","first-page":"419","article-title":"Differences in expression of lupus nephritis in New Zealand mixed H\u20102z homozygous inbred strains of mice derived from New Zealand black and New Zealand white mice. 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