This study investigates the prevalence and functional impact of single-base insertions (CEL-INS) in the variable number tandem repeat (VNTR) region of the carboxyl ester lipase (CEL) gene. The researchers found that these insertions are relatively common in the population and generally benign. Functional assays revealed that insertions in proximal VNTR repeats can lead to protein aggregation and endoplasmic reticulum stress. Notably, using a humanized CEL Knockin mouse model expressing the human CEL VNTR with 16 repeats, they observed somatic emergence of CEL-INS proteins in pancreatic tissue, suggesting that such insertions can arise spontaneously and may not be inherently pathogenic.
Single-base insertions in the CEL VNTR are common and typically benign. However, insertions in proximal repeats may lead to protein misfolding and stress responses. The humanized mouse model demonstrated that such insertions can arise somatically in the pancreas, indicating a potential mechanism for sporadic pancreatic dysfunction.
Humanized CEL Knockin mouse model, engineered to express the human CEL VNTR with 16 repeats, replacing the native mouse Cel VNTR, to study the expression and potential somatic emergence of CEL-INS proteins in vivo.
Pancreatic diseases, CEL gene, VNTR polymorphism, Protein misfolding, Somatic mutations
Humanized Knockin model, VNTR replacement, Protein aggregation studies, In vivo expression analysis
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
