{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:26:58Z","timestamp":1759134418030},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,3]],"date-time":"2005-02-03T00:00:00Z","timestamp":1107388800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>(SWR \u00d7 NZB)F<jats:sub>1<\/jats:sub> (or SNF<jats:sub>1<\/jats:sub>) hybrid mice succumb to lupus nephritis. A previous analysis of SNF<jats:sub>1<\/jats:sub> \u00d7 NZB backcross mice revealed the existence of 4 SWR loci (<jats:italic>H2<\/jats:italic> on chromosome 17, <jats:italic>Swrl\u20101<\/jats:italic> on chromosome 1, <jats:italic>Swrl\u20102<\/jats:italic> on chromosome 14, and <jats:italic>Swrl\u20103<\/jats:italic> on chromosome 18) and 2 NZB loci (<jats:italic>Nba1<\/jats:italic> and <jats:italic>Lbw2\/Sbw2<\/jats:italic>, both on chromosome 4). A second study focusing on SNF<jats:sub>1<\/jats:sub> \u00d7 SWR backcross offspring uncovered 5 suggestive loci for antinuclear antibody formation, consisting of 3 dominant NZB contributions (<jats:italic>Nba4<\/jats:italic> on chromosome 5, <jats:italic>Lbw4<\/jats:italic> on chromosome 6, and <jats:italic>Nba5<\/jats:italic> on chromosome 7) and 2 recessive SWR contributions (<jats:italic>Swrl\u20101<\/jats:italic> on chromosome 1 and <jats:italic>Swrl\u20104<\/jats:italic> on chromosome 10). The present intercross study was executed to replicate the earlier findings, using an independent panel of (SWR \u00d7 NZB)F<jats:sub>2<\/jats:sub> offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A panel of (NZB \u00d7 SWR)F<jats:sub>2<\/jats:sub> hybrids were phenotyped (for renal disease, early mortality, and a variety of autoantibodies) and genotyped (using 95 microsatellite primers positioned across all 19 autosomes and the X chromosome). Linkage analysis was conducted using the derived phenotype and genotype data, with the interval\u2010mapping program MapManager.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four suggestive loci were mapped: <jats:italic>Swrl\u20105<\/jats:italic> on chromosome 1 (peak at 106 cM), linked to hypergammaglobulinemia; an NZB locus on chromosome 5 (<jats:italic>Nba4<\/jats:italic>; peak at 15 cM), linked to IgG anti\u2013single\u2010stranded DNA (anti\u2010ssDNA) antibodies, IgG anti\u2013doubled\u2010stranded DNA (anti\u2010dsDNA) antibodies, and glomerulonephritis; an NZB locus on chromosome 13 (<jats:italic>Nba6<\/jats:italic>; peak at 28 cM), linked to IgG anti\u2010dsDNA antibodies; and an SWR locus on chromosome 14 (<jats:italic>Swrl\u20102<\/jats:italic>; peak at 30 cM), linked to IgG anti\u2010ssDNA antibodies. Eight additional loci revealed linkage at <jats:italic>P<\/jats:italic> &lt; 0.01, of which 7 co\u2010mapped with lupus susceptibility loci previously identified in other models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Considering all 3 mapping studies together, lupus in SWR\/NZB hybrids appears to be the epistatic end product of several distinct loci, of which 3 SWR\u2010derived loci (<jats:italic>Swrl\u20101, Swrl\u20102<\/jats:italic>, and <jats:italic>Swrl\u20103<\/jats:italic>) and 5 NZB\u2010derived loci (<jats:italic>Nba1<\/jats:italic>, <jats:italic>Nba3<\/jats:italic>, <jats:italic>Nba4<\/jats:italic>, <jats:italic>Nba5<\/jats:italic>, and <jats:italic>Lbw4<\/jats:italic>) have been independently confirmed. The immunologic functions and molecular identities of these loci await elucidation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20786","type":"journal-article","created":{"date-parts":[[2005,2,3]],"date-time":"2005-02-03T22:48:32Z","timestamp":1107470912000},"page":"659-667","source":"Crossref","is-referenced-by-count":10,"title":["Genetic origin of lupus in NZB\/SWR hybrids: Lessons from an intercross 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