Targeting Trysin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model
Technical Report,15 Sep 2016,14 Sep 2017
Cedars-Sinai Medical Center Los Angeles United States
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Acute pancreatitis especially due to alcohol and smoking goes onto chronic pancreatitis which, in turn, is a risk factor for pancreatic cancer. Because only a relatively small portion of patients with alcohol abuse and smoking develop pancreatitis, it is very likely that there are genetic underlying predisposing factors that have not been discovered that explain why certain individuals develop pancreatitis. A genetic defect in the trypsinogen gene PRSS1 gene causing hereditary pancreatitis is now well established. We developed a transgenic mouse using a Bacterial Artificial Chromosome harboring the full-length human PRSS1 with the key mutation of hereditary pancreatitis PRSS1R122H. During the funding year we used this novel mouse model to determine whether PRSS1R122H and heavy drinking and smoking predispose to pancreatitis. Our data so far indicates that mice expressing PRSS1R122H develop a more severe form of pancreatitis than wild type mice and recovery after pancreatitis is impaired. We are working now in understanding the mechanisms underlying the observed effects.
- Medicine and Medical Research