Abstract
Purpose :
The male Non-Obese Diabetic (NOD) mouse is an established model for the autoimmune dacryoadenitis characteristic of Sjögren’s Syndrome (SS), but development of diabetes may complicate studies. The Non-Obese Diabetes Resistant (NOR) mouse is a MHC-matched diabetes-resistant strain that provides an alternative, however, its development of autoimmune dacryoadenitis and other features of SS have not been well-characterized. Here, we compare features of SS in male NOD and NOR mice at 12 and 20 wks.
Methods :
Blood glucose and basal tear secretion in male NOD, NOR and BALB/c mice were measured between 10-20 wks of age. Stimulated tear secretion by topical carbachol application to lacrimal glands (LG) and measurement of tear cathepsin S (CTSS) activity was performed on separate cohorts at 12 and 20 wks. LGs were retrieved at 12 and 20 wks for histology,RT-qPCR analysis and immunostaining.
Results :
No differences in thread test or blood glucose values between BALB/c, NOD and NOR mice were seen from 10-20 wks. Stimulated tear secretion was significantly decreased at 12 wks in NOD (3.2±0.6 μl) relative to BALB/c (4.7±0.8 μl) (p<0.05), but not in NOR mice (4.0±1.2 μl). At 20 wks, both NOD (3.0± 0.6 μl, p<0.001) and NOR (3.3±0.7 μl, p<0.001) had significantly decreased stimulated tear volume relative to BALB/c mice (5.4± 0.6 μl). Tear CTSS activity was significantly elevated in NOD (159-fold at 12 wks, p<0.05; 56-fold at 20 wks, p<0.05) and NOR (203-fold at 12 wks, p<0.001; 81-fold at 20 wks,p<0.001) relative to BALB/c. While both NOD and NOR mouse LG showed a significant increase in the percentage of total LG area occupied by lymphocytes at 12 and 20 wks relative to BALB/c, the percentage in NOD mice was significantly increased also relative to NOR (p<0.01 at 12wks, p<0.05 at 20 wks) respectively. In NOD mouse LG, fold-change increases in expression of disease-related genes relative to BALB/c were: CTSS, 7.55 (p<0.001) at 12 wks and 8.77 (p<0.05) at 20 wks; MHCII ,58.42-fold (P<0.001) at 12 wks and 94.87-fold (P=0.07) at 20 wks; IFN-γ, 3.29-fold (p<0.05) at 12 wks and 15.25-fold (p<0.05) at 20 wks. No increases in expression of these genes was seen in NOR mice.
Conclusions :
While NOR and NOD mice share features of the autoimmune dacryoadenitis characteristic of SS, the NOD mouse exhibits a stronger disease phenotype and earlier disease onset in the absence of diabetes up to 20 wks.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.