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

Objective. To clarify the mode of inheritance of autoimmune sialadenitis in MRL/MpJ-lpr/lpr (MRL/ lpr) lupus-prone mice and identify the susceptibilit y loci. Methods. MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr)F-1 intercr oss, and MRL/lpr x (MRL/lpr x C3H/lpr)F-1 backcross mice were prepared, and sialadenitis in individual mice was analyzed by histopathologic grading. T he genomic DNA of the backcross mice was examined by simple sequence-length polymorphism analysis, and the highly associated polymorphic microsatellit e markers with sialadenitis were determined as sialadenitis susceptibility loci. Results, Four susceptible gene loci recessively associated with sialadeniti s were mapped on chromosomes 10, 18, 4, and 1, respectively. These loci man ifested additive and hierarchical properties in the development of sialaden itis. Conclusion. The results indicate that sialadenitis in MRL/lpr mice is under the control of polygenic inheritance, possibly involving allelic polymorph ism.