The CEL-HYB1 Hybrid Allele Promotes Digestive Enzyme Misfolding and Pancreatitis in Mice.

ABSTRACT:

Background & aims

A hybrid allele that originated from homologous recombination between CEL and its pseudogene (CELP), CEL-HYB1 increases the risk of chronic pancreatitis (CP). Although suggested to cause digestive enzyme misfolding, definitive in vivo evidence for this postulate has been lacking.

Methods

CRISPR-Cas9 was used to generate humanized mice harboring the CEL-HYB1 allele on a C57BL/6J background. Humanized CEL mice and C57BL/6J mice were used as controls. Pancreata were collected and analyzed by histology, immunohistochemistry, immunoblotting, and transcriptomics. Isolated pancreatic acini were cultured in vitro to measure the secretion and aggregation of CEL-HYB1 protein. Mice were given caerulein injections to induce acute pancreatitis (AP) and CP.

Results

SUBMITTER: Mao XT 

PROVIDER: S-EPMC9117557 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature