Experiment
Genome scan using 106 informative markers at an average spacing of 15 cM was performed on 106 female animals from a (NZM2328/J x C57L/J) x NZM2328/J backcross to map QTLs associated with systemic erythematosus (SLE) phenotypes. NZM2328/J females are highly susceptible to SLE and develop SLE phenotypes by 12 months of age. In contrast, C57L/J females do not show signs of SLE at 12 months of age. A significant locus associated with chronic glomerulonephritis and severe proteinuria in NZM2328/J mice, Cgnz1,was identified on distal mouse Chromosome 1 at approximately 92.3 cM (P = 0.000001 at D1Mit36). NZM2328/J alleles confer recessively inherited susceptibility to SLE at Cgnz1. Cgnz1 maps near Sle1, a QTL for SLE susceptibility, and may be identical to Sle1. Suggestive loci associated with acute glomerulonephritis in NZM2328 mice, which the authors name Agnz1 and Agnz2, mapped to distal mouse Chromosome 1 at approximately 101 cM (P = 0.0002 at D1Mit37) and mouse Chromosome 17 at approximately 55.7 cM (P = 0.0005at D17Mit130), respectively. Authors note Agnz1 is distinct from Cgnz1 on distal mouse Chromosome 1. A suggestive locus associated with recessively inherited susceptibility to anti-dsDNA antibody production in NZM2328/J mice, Adaz1, mapped to mouse Chromosome 4 at approximately 49.6 cM (P = 0.00018 at D4Mit175 and D4Mit187). Cgnz1 and Adaz1 were confirmed in congenic strains carrying C57L/J-derived DNA at Cgnz1 or Adaz1 on a NZM2328/J background. Heterozygosity at Gnz1 prevented proteinuria and chronic glomerulonephritis in animals congenic for the Chromosome 1 locus, and heterozygosity at Adaz1 reduced anti-dsDNA antibody production in animals congenic for the Chromosome 4 locus.
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