Authentic Mouse Model of PRSS1-Related Hereditary Pancreatitis
Abstract
Introduction. The most frequent cause of hereditary pancreatitis is the p.R122H mutation in the serine protease 1 (PRSS1) gene, which encodes human cationic trypsinogen. This mutation renders trypsinogen resistant to protective degradation by chymotrypsin and thereby results in elevated intrapancreatic trypsin activity that elicits pancreatitis. Methods. We introduced the p.R123H mutation, which is analogous to human PRSS1 mutation p.R122H, in the mouse cationic trypsinogen (isoform T7) and characterized the severity of experimentally induced acute pancreatitis in the novel T7R123H mice. Results. The T7R123H knock-in mouse strain developed no spontaneous pathology in the pancreas or elsewhere. When pancreatitis was induced experimentally by cerulein injections, T7R123H mice exhibited similar intrapancreatic trypsin activation and disease severity as C57BL/6N control mice treated in the same manner. Sustained stimulation with cerulein, however, resulted in more severe chronic pancreatitis in T7R123H mice than in C57BL/6N controls. Conclusion. The observations indicate that T7R123H mice exhibit more severe experimental pancreatitis in case of persistent pancreatic injury. The findings are consistent with the proposed pathogenic role of the p.R122H trypsinogen mutation in humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2022
- Accession Number
- AD1168127
Entities
People
- Miklós Sahin-Tóth
- Zsanett Jancso
Organizations
- University of California, Los Angeles