Genetic basis of tissue specificity of vasculitis in MRL/lpr mice
Copyright policy )Genetic basis of tissue specificity of vasculitis in MRL/lpr mice
AbstractObjectiveTo 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.MethodsVasculitis 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.ResultsA 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.ConclusionSystemic vasculitis in MRL/lpr mice is genetically controlled with cumulative effects of multiple gene loci, each of which has tissue specificity.
- Tohoku University Japan
- University of Tokyo Japan
- Ehime University Japan
Male, Vasculitis, Mice, Inbred C3H, Mice, Inbred MRL lpr, Quantitative Trait Loci, DNA, Polymerase Chain Reaction, Disease Models, Animal, Mice, Organ Specificity, Animals, Female, Genetic Predisposition to Disease, Lod Score, Aorta, Crosses, Genetic, Microsatellite Repeats
Male, Vasculitis, Mice, Inbred C3H, Mice, Inbred MRL lpr, Quantitative Trait Loci, DNA, Polymerase Chain Reaction, Disease Models, Animal, Mice, Organ Specificity, Animals, Female, Genetic Predisposition to Disease, Lod Score, Aorta, Crosses, Genetic, Microsatellite Repeats
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