• chronic pancreatitis

In Gut, Hegyi and Sahin-Tòth report the first reliable mouse model of chronic pancreatitis (CP).1 More than six decades ago, the first pedigree of a family with inherited CP was published. Nevertheless, it lasted until now that the first reliable animal model of the disease was established. Whereas the first genetic associations were found to reside in the cationic trypsinogen gene (PRSS1), Hegyi and Sahin-Tóth developed an animal model with the frequent p.N256K mutation in Carboxypeptidase A1 (CPA1).2 3 Besides PRSS1 alterations, mutations in CPA1 harbour the second largest effect size for the development of CP (see also http://www.pancreasgenetics.org/) and therefore represent reasonable candidates for an animal model. In addition, the detection of CPA1 mutations in CP provided new mechanistic insights into the pathogenesis, but also reinforced the current notion that digestive proteases play a critical role in CP. The presented model is a knock-in of the human mutation into the Cpa1 mouse locus and exhibits spontaneous hallmarks of CP like fibrosis and acinar-ductal metaplasia. …