Date of Award
Master of Science
Physiology and Pharmacology
Dr. Christopher Pin
Rodent models show that alcohol only sensitizes the pancreas to subsequent insult, indicating that additional factors play a role in alcohol-induced pancreatic injury. Mice lacking MIST1 (Misti4'), a target of the UPR marker XBP1, show reduced ability to activate the UPR during cell stress. Therefore, I hypothesized that an absence of MIST1 would lead to increased sensitivity to alcohol feeding. The effects of dietary stress on the UPR were examined in pancreatic tissue from 2 to 4 month-old mice placed on a diet containing 36% of kcal from ethanol for 6 weeks. Based on immunofluorescent, histological and immunoblotting assays, MistTAmice showed age related changes in UPR activation. In response to ethanol, they developed periductal accumulations of inflammatory cells, limited induction of autophagy and reduction in the expression of BiP, pelF2a and sXbp1, unlike wild type counterparts that had significantly higher levels of sXbp1 and pelF2a. The UPR was not further activated following initiation of acute pancreatitis. This work suggests that factors affecting MIST1 expression and function in humans may be a predisposing factor for pancreatic disease.
Alahari, Sruthi, "MICE LACKING MIST1 SHOW INCREASED SENSITIVITY TO CHRONIC ETHANOL EXPOSURE" (2011). Digitized Theses. 3416.