Dominant NZB contributions to lupus in the (SWR×NZB)F1 model

(SWR × NZB)F1 (or SNF1) mice succumb to lupus nephritis. Analysis of NZB × SNF1 backcross mice has recently revealed the existence of four dominant SWR loci (H2 on Chr 17, Swrl-1 on Chr 1, Swrl-2 on Chr 14 and Swrl-3 on Chr 18), and two NZB loci (Nba1 and Lbw2/Sbw2, both on Chr 4) conferring lupus susceptibility. The present study focusing on a panel of 88 SWR × SNF1 backcross mice reveals the existence of five suggestive loci for antinuclear antibody formation, consisting of three dominant NZB contributions (Nba4 on Chr 5, Lbw4 on Chr 6, and Nba5 on Chr 7), and two recessive SWR contributions (Swrl-1 on Chr 1, and Swrl-4 on Chr 10). In addition, this study reveals a dominant NZB locus for GN (Nba3 on Chr 7, peak at 31 cM), and a dominant NZB locus linked to early mortality, on Chr 10 (peak at 4 cM). Collectively, these studies suggest that lupus in the SNF1 strain is the epistatic end-product of four dominant SWR loci and four dominant NZB loci. The immunological functions and molecular identities of these loci await elucidation.