Genetic susceptibility is the major predisposing factor thus far identified for spontaneous systemic lupus erythematosus (SLE) in both humans and animal models of the disease. Previously, the investigator identified in an (NZB x NZW)F2 intercross 8 loci designated Lbw1-Lbw8 on chromosomes 17, 4, 5, 6, 7, 18, 1, and 11, respectively, that exhibited evidence of linkage to one or more of four major SLE disease traits. Five of these loci have been confirmed in other crosses. The investigator has generated congenic lines for Lbw2, a locus on chromosomes 4 required for hemolytic anemia, and Lbw5, a locus on chromosome 7. Lbw5 is an autoimmune accelerator that increases the production of IgG autoantibodies and promotes hemolytic anemia, glomerulonephritis and early mortality in NZB mice. In this application the investigator proposes to: 1) define the genetics of immunoglobulin and autoantibody responses and the relationship of autoantibody specificity to other traits. This will be done by linkage analysis using an expanded set of BWF2 mice; 2) generate congenic lines for Lbw1, 2, 4, 5 and 7 to examine the effects of susceptibility and resistance alleles at these loci on clinical and immunologic manifestations; and 3) undertake positional cloning of Lbw2 and Lbw5.
| Scatizzi, John C; Haraldsson, Maria K; Pollard, K Michael et al. (2012) The Lbw2 locus promotes autoimmune hemolytic anemia. J Immunol 188:3307-14 |
| Pollard, Kenneth M; Hultman, Per; Toomey, Christopher B et al. (2011) ?2-microglobulin is required for the full expression of xenobiotic-induced systemic autoimmunity. J Immunotoxicol 8:228-37 |
| Zuo, Li; Fulkerson, Patricia C; Finkelman, Fred D et al. (2010) IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha 2-inhibited pathway. J Immunol 185:660-9 |
| Arandjelovic, Sanja; Wickramarachchi, Dilki; Hemmers, Saskia et al. (2010) Mast cell function is not altered by Coronin-1A deficiency. J Leukoc Biol 88:737-45 |
| Pollard, K Michael; Hultman, Per; Kono, Dwight H (2010) Toxicology of autoimmune diseases. Chem Res Toxicol 23:455-66 |
| Aït-Azzouzene, Djemel; Kono, Dwight H; Gonzalez-Quintial, Rosana et al. (2010) Deletion of IgG-switched autoreactive B cells and defects in Fas(lpr) lupus mice. J Immunol 185:1015-27 |
| Kono, Dwight H; Haraldsson, M Katarina; Lawson, Brian R et al. (2009) Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus. Proc Natl Acad Sci U S A 106:12061-6 |
| Haraldsson, M Katarina; Louis-Dit-Sully, Christine A; Lawson, Brian R et al. (2008) The lupus-related Lmb3 locus contains a disease-suppressing Coronin-1A gene mutation. Immunity 28:40-51 |
| Santiago-Raber, Marie-Laure; Haraldsson, M Katarina; Theofilopoulos, Argyrios N et al. (2007) Characterization of reciprocal Lmb1-4 interval MRL-Faslpr and C57BL/6-Faslpr congenic mice reveals significant effects from Lmb3. J Immunol 178:8195-202 |
| Kono, Dwight H; Theofilopoulos, Argyrios N (2006) Genetics of SLE in mice. Springer Semin Immunopathol 28:83-96 |
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