Preclinical mouse model of a misfolded PNLIP variant develops chronic pancreatitis.

ABSTRACT:

Objective

Increasing evidence implicates mutation-induced protein misfolding and endoplasm reticulum (ER) stress in the pathophysiology of chronic pancreatitis (CP). The paucity of animal models harbouring genetic risk variants has hampered our understanding of how misfolded proteins trigger CP. We previously showed that pancreatic triglyceride lipase (PNLIP) p.T221M, a variant associated with steatorrhoea and possibly CP in humans, misfolds and elicits ER stress in vitro suggesting proteotoxicity as a potential disease mechanism. Our objective was to create a mouse model to determine if PNLIP p.T221M causes CP and to define the mechanism.

Design

We created a mouse model of Pnlip p.T221M and characterised the structural and biochemical changes in the pancreas aged 1-1

SUBMITTER: Zhu G 

PROVIDER: S-EPMC10257759 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature