{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:41:03Z","timestamp":1785894063265,"version":"3.56.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The observation that<jats:italic>Borrelia burgdorferi<\/jats:italic>-induced arthritis is severe in C3H mice and milder in C57BL\/6 (B6) mice has allowed a forward genetics approach for the identification of genetic elements that regulate the arthritis response. Quantitative trait loci (QTL) on five chromosomes (Chr) were identified previously in segregating crosses between C3H and B6 mice and collectively designated<jats:italic>B. burgdorferi<\/jats:italic>arthritis-associated (<jats:italic>Bbaa<\/jats:italic>) QTL. Reciprocal interval-specific congenic lines (ISCL) that encompass<jats:italic>Bbaa1<\/jats:italic>,<jats:italic>Bbaa2<\/jats:italic>-<jats:italic>Bbaa3<\/jats:italic>,<jats:italic>Bbaa4<\/jats:italic>,<jats:italic>Bbaa6<\/jats:italic>, and<jats:italic>Bbaa12<\/jats:italic>on Chr 4, 5, 11, 12, and 1, respectively, have now been generated. Bidirectional transfer of the arthritis severity phenotype in association with<jats:italic>Bbaa2<\/jats:italic>-<jats:italic>Bbaa3<\/jats:italic>and<jats:italic>Bbaa4<\/jats:italic>was observed, and unidirectional transfer with the B6 allele of<jats:italic>Bbaa6<\/jats:italic>was noted. These findings confirm the existence of polymorphic loci within<jats:italic>Bbaa2<\/jats:italic>-<jats:italic>Bbaa3<\/jats:italic>,<jats:italic>Bbaa4<\/jats:italic>, and<jats:italic>Bbaa6<\/jats:italic>that regulate the severity of<jats:italic>B. burgdorferi<\/jats:italic>-induced arthritis. ISCL were used to assess the regulation of a previously identified interferon transcriptional profile associated with severe disease in C3H mice. The regulation of this transcriptional signature was found to be independent of penetrant<jats:italic>Bbaa<\/jats:italic>QTL, both in joint tissues and in isolated macrophages. These results clearly demonstrate the utility of forward genetics for the discovery of novel genes and pathways involved in the regulation of the severity of Lyme arthritis and predict the involvement of regulatory elements not evident from other experimental approaches.<\/jats:p>","DOI":"10.1128\/iai.00396-09","type":"journal-article","created":{"date-parts":[[2009,6,2]],"date-time":"2009-06-02T00:58:56Z","timestamp":1243904336000},"page":"3302-3311","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Interval-Specific Congenic Lines Reveal Quantitative Trait Loci with Penetrant Lyme Arthritis Phenotypes on Chromosomes 5, 11, and 12"],"prefix":"10.1128","volume":"77","author":[{"given":"Ying","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary","family":"Crandall","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakumari","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Zachary","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pathology, University of Vermont, Burlington, Vermont 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Teuscher","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis J.","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/162.1.133"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1992.47.605"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.11.5208-5214.1998"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.5.2065-2071.1998"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.10.5142-5150.1999"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm961"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7043737"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199912)42:12<2705::AID-ANR29>3.0.CO;2-H"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00591a005"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg410"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.7930"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62050-0"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01078-08"},{"key":"e_1_3_2_15_2","first-page":"241","volume":"10","year":"2009","unstructured":"Frazer, K. 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