Authentic Mouse Model of PRSS1 Related Hereditary Pancreatitis
Abstract
The most frequent cause of hereditary pancreatitis is the R122H mutation in cationic trypsinogen (PRSS1). This mutation renders trypsinogen resistant to protective degradation by chymotrypsin-dependent mechanisms and thereby results in elevated intra-pancreatic trypsin activity. Methods. We introduced the p.R123H mutation, which is analogous to human PRSS1 mutation p.R122H, in the mouse T7 trypsinogen gene and characterized acute pancreatitis responses elicited with repetitive cerulein injections. Results. The T7R123H knock-in strain developed no spontaneous pathology in the pancreas or elsewhere. When given cerulein, T7R123H mice exhibited higher pancreatic edema and inflammatory cell infiltration, compared with C57BL/6N control mice treated in the same manner. Conclusion. The observations indicate that the R123H mutation in mouse cationic trypsinogen is insufficient to elicit pancreatitis but it sensitizes the pancreas to harmful stimuli and heighten pathological responses in the secretagouge-induced pancreatitis model in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2021
- Accession Number
- AD1129014
Entities
People
- Zsanett Jancso
Organizations
- University of California, Los Angeles