Targeting Trypsin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model
Technical Report,15 Sep 2015,14 Sep 2019
Mayo Clinic Jacksonville United States
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Pancreatitis is an inflammatory disease that may be initiated by lifestyle factors such as alcohol abuse, smoking or high fat diet. Acute pancreatitis can become chronic, which is a primary risk factor for developing pancreatic cancer. Since only a fraction of patients that develop pancreatitis report alcohol abuse or smoking, it is very likely that there are also underlying genetic factors for this condition. A well-established genetic defect R122H in the trypsinogen gene PRSS1 results in the development of hereditary pancreatitis. We developed a transgenic mouse model to study the key mutation found in patients with hereditary pancreatitis PRSS1-R122H. During the final funding year we evaluated whether this novel mouse model predisposed animals to pancreatitis. Our current data show that mice expressing PRSS1-R122H develop a more severe form of pancreatitis than their wild-type littermates, shown by higher serum amylase levels. The addition of sex hormones resulted in no significant difference in pancreatic weight or animal health. Anti-hormone studies generated no differences in pancreatitis compared to the control group. Finally, chemical chaperone studies to reduce pancreatitis in these mice were not able to be carried out to completion due to technical difficulties.
- Medicine and Medical Research