Genetic contributions of nonautoimmune SWR mice toward lupus nephritis

S. Xie, S. Chang, P. Yang, C. Jacob, A. Kaliyaperumal, S. K. Datta, C. Mohan*

*Corresponding author for this work

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20 Scopus citations

Abstract

(SWR x New Zealand Black (NZB))F1 (or SNF1) mice succumb to lupus nephritis. Although several NZB lupus susceptibility loci have been identified in other crosses, the potential genetic contributions of SWR to lupus remain unknown. To ascertain this, a panel of 86 NZB x F1 backcross mice was immunophenotyped and genome scanned. Linkage analysis revealed four dominant SWR susceptibility loci (H2, Swrl-1, Swrl-2, and Swrl-3) and a recessive NZB locus, Nba1. Early mortality was most strongly linked to the H2 locus on chromosome (Chr) 17 (log likelihood of the odds (LOD) = 4.59 - 5.38). Susceptibility to glomerulonephritis was linked to H2 (Chr 17, LOD = 2.37 - 2.70), Swrl-2 (Chr 14, 36 cM, LOD = 2.48 - 2.71), and Nba1 (Chr 4, 75 cM, LOD = 2.15 - 2.23). IgG antinuclear autoantibody development was linked to H2 (Chr 17, LOD = 4.92 - 5.48), Swrl-1 (Chr 1, 86 cM, colocalizing with Sle1 and Nba2, LOD = 2.89 - 2.91), and Swrl-3 (Chr 18, 14 cM, LOD = 2.07 - 2.13). For each phenotype, epistatic interaction of two to three susceptibility loci was required to attain the high penetrance levels seen in the SNF1 strain. Although the SWR contributions H2, Swrl-1, and Swrl-2 map to loci previously mapped in other strains, often linked to very similar phenotypes, Swrl-3 appears to be a novel locus. In conclusion, lupus in the SNF1 strain is truly polygenic, with at least four dominant contributions from the SWR strain. The immunological functions and molecular identities of these loci await elucidation.

Original languageEnglish (US)
Pages (from-to)7141-7149
Number of pages9
JournalJournal of Immunology
Volume167
Issue number12
DOIs
Publication statusPublished - Dec 15 2001

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ASJC Scopus subject areas

  • Immunology

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Xie, S., Chang, S., Yang, P., Jacob, C., Kaliyaperumal, A., Datta, S. K., & Mohan, C. (2001). Genetic contributions of nonautoimmune SWR mice toward lupus nephritis. Journal of Immunology, 167(12), 7141-7149. https://doi.org/10.4049/jimmunol.167.12.7141