Year: 2014
Type: article
Abstract: Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients.
Source: American Journal Of Pathology
Authors: Xingshen Sun, Alicia K. Olivier, Yaling Yi, Christopher E. Pope, Hillary S. Hayden, Bo Liang, Hongshu Sui, Weihong Zhou, Kyle R. Hager, Yulong Zhang, Xiaoming Liu, Ziying Yan, John T. Fisher, Nicholas W. Keiser, Yi Song, Scott R. Tyler, J. Adam Goeken, Joann M. Kinyon, Matthew C. Radey, Danielle Fligg, Xiaoyan Wang, Weiliang Xie, Thomas J. Lynch, Paul M. Kaminsky, Mitchell J. Brittnacher, Samuel I. Miller, Kalpaj Parekh, David K. Meyerholz, Lucas R. Hoffman, Timothy Frana, Zoe A. Stewart, John F. Engelhardt
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,800
Awards: G1219496881, G1335906660, G2593938437, G3005125101, G308544354, G3185723841, G336615015, G4822469114, Pseudomonas Aeruginosa Early CF Adaptive Changes: A Translational Study, G5798220538, Medical Scientist Training Program, Center for Cystic Fibrosis Translational Research in the Post-CFTR modulator Era, Precision Medicine Center for Cystic Fibrosis, Pathobiology of Cystic Fibrosis-Related Diabetes in a Ferret Model
OpenAlex ID: W2145632758