Mouse Model of Human Hereditary Pancreatitis
Abstract
The aim of our research is to generate and characterize mouse models of human hereditary pancreatitis that develop pancreatitis spontaneously or exhibit increased sensitivity to experimentally induced pancreatitis. Such models are desperately needed to study in vivo the mechanistic aspects of the trypsin-dependent pathway in pancreatitis and to begin testing therapeutic and preventive approaches. Mutations in the digestive enzyme trypsinogen cause hereditary pancreatitis in humans. Previous attempts to introduce these mutant forms of human trypsinogen into mice have failed to produce models that recapitulate the human disease. Therefore, we introduced mutations in the endogenous mouse T7 cationic trypsinogen gene and obtained several new strains carrying mutations D23A, D23del or K24R. Remarkably, mice with the D23A mutation develop spontaneous, progressive pancreatitis with eventual destruction and fatty replacement of the exocrine pancreas and preservation of endocrine tissue. On the other hand, mouse strains carrying the D23del or K24R mutations do not develop spontaneous pancreatitis but may be more susceptible to experimentally induced pancreatitis. These novel models will afford important insight into the role of trypsin in human hereditary pancreatitis and facilitate testing of trypsin inhibition as a therapeutic approach.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1020583
Entities
People
- Miklós Sahin-Tóth