Endocrine pathology in young rabbits with cystic fibrosis

Abstract

Background Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the CF transmembrane conductance regulator gene. CF-related pancreatic lesions are known to cause exocrine dysfunctions such as pancreatic insufficiency, and endocrine dysfunctions, including CF-related diabetes. In a previous study, we generated rabbits with CF using CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)-mediated gene editing.Methods Rabbits with CF were subjected to histological analysis with a focus on CF-associated pancreatic lesions. Endocrine function-related assays were conducted to evaluate CF-related pancreatic endocrine disorders in these animals.Results We report that rabbits with CF develop spontaneous pancreatic lesions at a young age, characterised by pancreatic inflammation and fibrosis, vacuolar degeneration, epithelium mucus-secretory cell metaplasia and pancreatic duct dilation. The size of the pancreatic islets in the rabbits with CF is significantly smaller than that of the wild-type animals. Consistent with these pathological findings, young rabbits with CF exhibited signs of pancreatic endocrine-related disorders such as lower insulin levels and impaired glucose metabolism.Conclusions Our results suggest that the CF rabbit could serve as a valuable model for translational research on CF-related pancreatic endocrine dysfunction.