Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72(c) allele

An MRL/MpJ strain of mice bearing the Fas deletion mutant gene, Ipr (MRL/Ip r), composed of genomes derived from LG/J, AKR/J, C3H/Di and C57BL/6J mice, develops systemic vasculitis coincidentally with other collagen diseases, but a C3H/HeJ-Ipr/Ipr (C3H/Ipr) strain does not. In a genome-wide screening of the MRL background genes mediating susceptibility to collagen diseases using N2 progeny mice MRL/Ipr x (MRL/Ipr x C3H/Ipr)F1, we previously found that each collagen disease is controlled by a different set of genes. To cl arify the candidate genes for vasculitis, we extended the linkage analysis of renal vasculitis to a larger number of N2 mice and to F2 intercross mice . Two distinct recessive susceptibility loci for vasculitis were mapped on chromosome (Chr) 4 at D4Mit89 and D4Mit147 in both progenies. The former wa s a novel locus for lupus phenotypes, which involved the MRL allele CD72 de grees in contrast to the C3H allele CD72(b). The one on Chr 3 was a recessi ve locus which had an inhibitory effect on vasculitis. From their compositi on these loci seemed to be derived from AKR/J (for one) and LG/J (for anoth er two) strains, and appeared to act in an additive manner on the developme nt of vasculitis, indicating that vasculitis in MRL/Ipr mice is inherited i n a polygenic manner.