Epistatic modifiers of autoimmunity in a murine model of lupus nephritis

Laurence Morel, Xiang Hong Tian, Byron P. Croker, Edward K. Wakeland

Research output: Contribution to journalArticle

159 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalImmunity
Volume11
Issue number2
DOIs
StatePublished - Aug 1999

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Lupus Nephritis
Autoimmunity
Genome
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Epistatic modifiers of autoimmunity in a murine model of lupus nephritis. / Morel, Laurence; Tian, Xiang Hong; Croker, Byron P.; Wakeland, Edward K.

In: Immunity, Vol. 11, No. 2, 08.1999, p. 131-139.

Research output: Contribution to journalArticle

Morel, Laurence ; Tian, Xiang Hong ; Croker, Byron P. ; Wakeland, Edward K. / Epistatic modifiers of autoimmunity in a murine model of lupus nephritis. In: Immunity. 1999 ; Vol. 11, No. 2. pp. 131-139.
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