Epistatic suppression of systemic lupus erythematosus: Fine mapping of Sles1 to less than 1 Mb

Srividya Subramanian, Young Sun Yim, Kui Liu, Katalin Tus, Xin J. Zhou, Edward K. Wakeland

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Abstract

Sle is a susceptibility locus for systemic autoimmunity derived from the lupus-prone NZM2410 mouse. The New Zealand White-derived suppressive modifier Sles1 was identified as a specific modifier of Sle1 and prevents the development of IgG anti-chromatin autoantibodies mediated by Sle1 on the C57BL/6 (B6) background. Fine mapping of Sles1 with truncated congenic intervals localizes it to a ∼956-kb segment of mouse chromosome 17. Sles1 completely abrogates the development of activated T and B cell populations in B6.Sle1, Despite this suppression of the Sle1-mediated cell surface activation phenotypes, B6.Sle1 Sles1 splenic B cells still exhibit intrinsic ERK phosphorylation. Classic genetic complementation tests using the nonautoimmmune 129/SvJ mouse suggests that this strain possesses a Sles1 allele complementary to that of New Zealand White, as evidenced by the lack of glomerulonephritis, splenomegaly, and antinuclear autoantibody production seen in (129 × E6.Sle1 Sles1)F 1s. These findings localize and characterize the suppressive properties of Sles1 and implicate 129 as a useful strain for aiding in the identification of this elusive epistatic modifier gene.

Original languageEnglish (US)
Pages (from-to)1062-1072
Number of pages11
JournalJournal of Immunology
Volume175
Issue number2
Publication statusPublished - Jul 15 2005

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ASJC Scopus subject areas

  • Immunology

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Subramanian, S., Yim, Y. S., Liu, K., Tus, K., Zhou, X. J., & Wakeland, E. K. (2005). Epistatic suppression of systemic lupus erythematosus: Fine mapping of Sles1 to less than 1 Mb. Journal of Immunology, 175(2), 1062-1072.