Date of Award
Bachelor of Science
The salivary gland produces saliva that aids in digestion and in maintaining homeostasis in the oral cavity. Saliva production is disrupted in Sjögren’s Syndrome (SS), where the salivary gland is attacked by the immune system, leading to loss of function and hyposalivation. SS is thought to be accompanied by changes in the salivary epithelium, which are incompletely understood. In this study we have used the non-obese diabetic (NOD) mouse as a model for SS to study the changes in salivary gland epithelium, as these models present autoantibodies and other characteristics such as immune infiltrates similar to those found in SS patients. To quantify and explore glandular changes in both mouse and human tissue, epithelial proteins marking specific cell types were compared using multiplexed immunohistochemistry and immunofluorescent microscopy. Epithelial markers were characterized in human SS and two types of human control tissue, autopsy, and non-SS biopsies, and these results were compared to NOD epithelial tissue and healthy CD-1 age-matched controls. Specific protein markers used included cytokeratin 7 for ductal cells, cytokeratin 5 for undifferentiated progenitor cells, aquaporin 5 (AQP5) for acinar cells, smooth muscle α-actin for myoepithelial cells, and a small panel of innervation specific markers. In order to determine the effect of disease progression over time on the submandibular salivary epithelium, protein level and localization were compared between SS-like NOD tissue and CD-1 age-matched control tissues. Changes in protein levels were quantified using specialized quantitative immunohistochemistry, incorporating newly developed protocols. In order to evaluate the efficacy of the NOD mouse model as a model for human disease, mouse tissues were compared to human SS and control tissues. We conclude that while SS-like disease progression in the NOD mouse model occurs over time, the phenotype of the gland at time points previously characterized as late-stage disease may represent an earlier phenotype of diagnosed human SS, which is typically detected at a late stage.
Pagendarm, Nicholas, "Changes in Expression of Innervation and Accompanying Epithelium within Sjögren's Syndrome NOD/ShiLtJ Mouse Model" (2016). Biological Sciences. 35.