Mouse Model of Human Hereditary Pancreatitis
Annual rept. 1 Sep 2014-31 Aug 2015
TRUSTEES OF BOSTON UNIV MA
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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 have used mutated mouse trypsinogens that behave similarly to their human counterpart to create genetically altered mouse strains to model human hereditary pancreatitis. Specifically, we introduced mutations in the endogenous mouse T7 cationic trypsinogen gene and obtained several new mutant strains. These newly created mouse strains will be characterized with respect to spontaneous pancreatitis and sensitivity to experimentally induced pancreatitis. These studies are expected to lead to the development of novel therapeutic and preventive approaches using the novel mouse strains as test models.
- Medicine and Medical Research