ArticlePancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]2022
The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis in mice.
Article in Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- MisfoldingAmerican journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Chymotrypsin B2 (CTRB2) Deletion Variant Induces Endoplasmic Reticulum Stress but does not Increase Risk for Chronic Pancreatitis.Pancreas · 2025Article
- Overexpression of Tn antigen induces chronic pancreatitis in mice.Scientific reports · 2025Article
- Misfolding PRSS1 variant p.Ala61Val in a case of suspected intrauterine pancreatitis.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2025Article
- Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis.Scientific reports · 2024Article
- Novel chymotrypsin C (CTRC) variants from real-world genetic testing of pediatric chronic pancreatitis cases.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2024Article
- Exploring the enigmatic association between PNLIP variants and risk of chronic pancreatitis in a large Chinese cohort.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2024Article
- Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas.Human molecular genetics · 2024Article
- Characterization of novel PNLIP variants in congenital pancreatic lipase deficiency.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Article
- Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe CEL gene encodes the digestive enzyme carboxyl ester lipase. CEL-HYB1, a hybrid allele of CEL and its adjacent pseudogene CELP, is a genetic variant suggested to increase the risk of chronic pancreatitis (CP). Our aim was to develop a mouse model for CEL-HYB1 that enables studies of pancreatic disease mechanisms.
methodsWe established a knock-in mouse strain where the variable number of tandem repeat (VNTR) region of the endogenous mouse Cel gene was substituted with the mutated VNTR of the human CEL-HYB1 allele. Heterozygous and homozygous Cel-HYB1 mice and littermate wildtype controls were characterized with respect to pancreatic pathology and function.
resultsWe successfully constructed a mouse model with pancreatic expression of a humanized CEL-HYB1 protein. The Cel-HYB1 mice spontaneously developed features of CP including inflammation, acinar atrophy and fatty replacement, and the phenotype became more pronounced as the animals aged. Moreover, Cel-HYB1 mice were normoglycemic at age 6 months, whereas at 12 months they exhibited impaired glucose tolerance. Immunostaining of pancreatic tissue indicated the formation of CEL protein aggregates, and electron microscopy showed dilated endoplasmic reticulum. Upregulation of the stress marker BiP/GRP78 was seen in pancreatic parenchyma obtained both from Cel-HYB1 animals and from a human CEL-HYB1 carrier.
conclusionsWe have developed a new mouse model for CP that confirms the pathogenicity of the human CEL-HYB1 variant. Our findings place CEL-HYB1 in the group of genes that increase CP risk through protein misfolding-dependent pathways.
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