Genetic basis of autoimmune sialadenitis in MRL/lpr lupus-prone mice: Additive and hierarchical properties of polygenic inheritance

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Abstract
Objective To clarify the mode of inheritance of autoimmune sialadenitis in MRL/MpJ-lpr/lpr (MRL/lpr) lupus-prone mice and identify the susceptibility loci. Methods MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr × C3H/lpr)F1 intercross, and MRL/lpr × (MRL/lpr × C3H/lpr)F1 backcross mice were prepared, and sialadenitis in individual mice was analyzed by histopathologic grading. The genomic DNA of the backcross mice was examined by simple sequence-length polymorphism analysis, and the highly associated polymorphic microsatellite markers with sialadenitis were determined as sialadenitis susceptibility loci. Results Four susceptible gene loci recessively associated with sialadenitis were mapped on chromosomes 10, 18, 4, and 1, respectively. These loci manifested additive and hierarchical properties in the development of sialadenitis. Conclusion The results indicate that sialadenitis in MRL/lpr mice is under the control of polygenic inheritance, possibly involving allelic polymorphism.