Human CPA1 mutation causes digestive enzyme misfolding and chronic pancreatitis in mice.

ABSTRACT:

Objective

Chronic pancreatitis is a progressive, relapsing inflammatory disorder of the pancreas, which often develops in the background of genetic susceptibility. Recently, loss-of-function mutations in CPA1, which encodes the digestive enzyme carboxypeptidase A1, were described in sporadic early onset cases and in hereditary pancreatitis. Mutation-induced misfolding of CPA1 and associated endoplasmic reticulum (ER) stress was suggested as potential disease mechanism; however, in vivo evidence has been lacking. The objective of the present study was to create a mouse model that recapitulates features of CPA1-associated chronic pancreatitis.

Design

We knocked-in the most frequently occurring p.N256K human CPA1 mutation to the mouse Cpa1 locus. Mut

SUBMITTER: Hegyi E 

PROVIDER: S-EPMC6326849 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature