Genetic dissociation of dacryoadenitis and sialadenitis in a Sjogren's syndrome mouse model with common and different susceptibility gene loci.

PURPOSE: Sjögren's syndrome (SS) is a systemic autoimmune disease in which the main lesions are dacryoadenitis and sialadenitis. It is unclear whether these lesions develop in a common genetic background. A quantitative trait locus (QTL) analysis was performed in the SS mouse model, MRL/MpJ-lpr/lpr (MRL/lpr), to identify the susceptibility loci to dacryoadenitis and sialadenitis and the association with both loci.

METHODS: MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr) F1, and (MRL/lpr x C3H/lpr) F2 intercross mice were prepared, and the severity of dacryoadenitis and sialadenitis in individuals was quantified by histopathologic grading. In genomic DNA samples from the F2 mice, the polymorphic microsatellite markers highly associated with each lesion were determined as susceptibility loci.

RESULTS: QTLs with significant linkage for dacryoadenitis were mapped on chromosome 1 (the position of maximum logarithm of odds [LOD] score; 64.1 cM), designated Adacm1; chromosome 2 (88.4 cM), Adacm2; and chromosome 5 (63.9 cM), Adacm3. Those for sialadenitis were mapped on chromosome 1 (69.0 cM), Asm3, and chromosome 2 (65.3 cM and 82.1 cM), Asm4 and Asm5. Adacm1/Asm3 and Adacm2/Asm5 seemed to be a common chromosomal region, respectively. MRL-homozygous at Adacm1 and Adacm2 and at Asm3 and Asm5 manifested an additive effect on the development of dacryoadenitis and sialadenitis, respectively, whereas Adacm3 did not.

CONCLUSIONS: Dacryoadenitis and sialadenitis in MRL/lpr mice are under the control of common and different susceptibility loci, with an allelic combination that leads to regular variations in pathologic phenotypes.