Diverse Misfolding Mutant Digestive Enzymes Cause Chronic Pancreatitis Through Common Pathways.

ABSTRACT:

Background & aims

Increasing evidence suggests that protein misfolding and proteotoxicity is an important mechanism of chronic pancreatitis (CP) in patients with genetic variants. Two mouse models carrying misfolding digestive enzyme variants, CPA1 N256K and PNLIP T221M, recapitulate the human CP phenotype. We hypothesized that both models develop CP through similar disease mechanisms.

Methods

We conducted a comprehensive analysis of mice aged 1 to 6 months using histology, immunohistochemistry, protein immunoblotting, quantitative polymerase chain reaction (qPCR), transmission electron microscopy (TEM), and RNA sequencing (RNA-seq) analysis to characterize pancreatic pathological changes.

Results

Both homozygous models exhibited CP hallmarks, including progressive ac

SUBMITTER: Wilhelm SJ 

PROVIDER: S-EPMC12681743 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature