Genetic basis of tissue specificity of vasculitis in MRL/lpr mice

Abstract

Objective: To clarify the mode of inheritance of the tissue distribution of vasculitis in MRL/Mp‐lpr/lpr (MRL/lpr) lupus‐prone mice and to identify the susceptibility loci.Methods: Vasculitis in individual MRL/lpr, C3H/HeJ‐lpr/lpr (C3H/lpr), (MRL/lpr × C3H/lpr)F₁, and (MRL/lpr × C3H/lpr)F₂ intercross mice was analyzed by histopathologic grading of main branches of the aorta and of medium‐sized arteries in the lower limbs. Genomic DNA samples from F₂ intercross mice were examined by simple sequence‐length polymorphism analysis, and the polymorphic microsatellite markers highly associated with vasculitis in each tissue were determined as vasculitis susceptibility loci.Results: A susceptibility locus with significant linkage to vasculitis of main branches of the aorta was mapped on chromosome 4 at D4Mit213 (map position 13.3cM) selectively in males, while vasculitis of medium‐sized arteries in the lower limbs was mapped to different chromosomes: at D8Mit31 on chromosome 8 (map position 33.0) selectively in females and at D5Mit36 on chromosome 5 (map position 65.0). All of these were different from the previously defined loci governing susceptibility to vasculitis involving the kidneys.Conclusion: Systemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.