title: Epistatic modifiers of autoimmunity in a murine model of lupus nephritis.
abstract: Sle1 and Sle3 are NZW-derived loci that mediate lupus nephritis on a C57BL/6 background. The absence of severe autoimmunity in NZW suggests that the NZW genome suppresses these genes. (B6.NZMc1[Sle1] x NZW)F1 hybrids develop severe humoral autoimmunity and fatal lupus nephritis, indicating that suppression of Sle1 from NZW is recessive. Linkage analysis identified four epistatic modifiers, Sles1-4, whose cumulative effect accounted for the benign autoimmunity in NZW. The specific suppression of Sle1 but not Sle2 or Sle3 by Sles1 was directly demonstrated via the production and analysis of bicongenic strains. Moreover, Sles1 was sufficient to completely suppress autoimmunity initiated by Sle1 in B6.NZMc1 x NZW hybrids. These results demonstrate the complex epistatic interactions of loci augmenting and suppressing systemic autoimmunity.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville 32610, USA. morel.pathology@mail.health.ufl.edu
authors.forename: L
authors.initials: L
authors.lastname: Morel
authors.forename: X H
authors.initials: XH
authors.lastname: Tian
authors.forename: B P
authors.initials: BP
authors.lastname: Croker
authors.forename: E K
authors.initials: EK
authors.lastname: Wakeland
mesh_terms: D000483:Alleles; D000818:Animals; D015551:Autoimmunity / Q000235:genetics*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB
chemical_list: D006183:H-2 Antigens