Polygenic control of susceptibility to murine systemic lupus erythematosus

Laurence Morel, Ulrich H. Rudofsky, Jeffrey A. Longmate, Joel Schiffenbauer, Edward K. Wakeland

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Abstract

Susceptibility to glomerulonephritis (GN) and anti-dsDNA autoantibody production was analyzed in crosses with a newly developed systemic lupus erythematosus-susceptible inbred strain, MZM/Aeg2410. The mode of inheritance and the number and location of systemic lupus erythematosus-associated susceptibility loci were analyzed by interval mapping in a backcross with C57BL/6. Three chromosomal intervals containing strong recessive GM susceptibility alleles were identified on chromosomes 1, 4, and 7, each containing several potentially interesting candidate genes. Heterozygosity at H-2 was also found to correlate strongly with GN susceptibility, consistent with previous findings in the NZB/NZW parental strain model. Logistic regression analysis indicated that each of these susceptibility alleles independently accounted for a component of GN susceptibility, and that susceptibility was inherited as a threshold genetic liability in this model system.

Original languageEnglish (US)
Pages (from-to)4047-4057
Number of pages11
JournalJournal of Immunology
Volume195
Issue number9
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Morel, L., Rudofsky, U. H., Longmate, J. A., Schiffenbauer, J., & Wakeland, E. K. (2015). Polygenic control of susceptibility to murine systemic lupus erythematosus. Journal of Immunology, 195(9), 4047-4057.