Vasculitis-susceptible genes in mice with a deficit in Fas-mediated apoptosis

Autoimmune diseases show complex pathological manifestations, which frequen tly involve systemic vasculitis. This complication is understood to be a ma nifestation of advanced disease, or to represent distinct entities, restric ted by genetic and/or environmental factors. An MRL/Mp strain of mice beari ng the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop syste mic vasculitis coincidentally with glomerulonephritis, arthritis and sialoa denitis, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. Thus, this is a s uitable model for analyzing the genetic basis of vasculitis in autoimmune d iseases. To genetically dissect these complex pathological manifestations, a linkage analysis of each lesion with polymorphic microsatellite markers w as performed by using MRL/lplx(MRL/lprxC3H/lpr)F1 backcross mice. Vasculiti s-susceptible gene loci were mapped on chromosomes 3 and 4, which were not associated with glomerulonephritis, arthritis and sialoadenitis. These resu lts indicate that systemic vasculitis in MRL/lpr mice may be under the cont rol of host genes which are different from those for other autoimmune disea ses. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.