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 exocrin...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.展开更多
基金supported by National Institutes of Health grants DK134361(to KZ and JX).
文摘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.
