Journal article
Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets
The American journal of pathology, Vol.184(5), pp.1309-1322
05/2014
DOI: 10.1016/j.ajpath.2014.01.035
PMCID: PMC4005986
PMID: 24637292
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.
Details
- Title: Subtitle
- Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets
- Creators
- Xingshen Sun - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaAlicia K Olivier - Department of Pathology, University of Iowa, Iowa City, IowaYaling Yi - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaChristopher E Pope - Department of Pediatrics, University of Washington, Seattle, Washington; Department of Microbiology, University of Washington, Seattle, WashingtonHillary S Hayden - Department of Microbiology, University of Washington, Seattle, WashingtonBo Liang - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaHongshu Sui - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaWeihong Zhou - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaKyle R Hager - Department of Microbiology, University of Washington, Seattle, WashingtonYulong Zhang - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaXiaoming Liu - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaZiying Yan - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaJohn T Fisher - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaNicholas W Keiser - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaYi Song - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaScott R Tyler - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaJ Adam Goeken - Department of Pathology, University of Iowa, Iowa City, IowaJoann M Kinyon - Department of Veterinary Diagnostic & Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IowaMatthew C Radey - Department of Microbiology, University of Washington, Seattle, WashingtonDanielle Fligg - Department of Veterinary Diagnostic & Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IowaXiaoyan Wang - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaWeiliang Xie - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaThomas J Lynch - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaPaul M Kaminsky - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IowaMitchell J Brittnacher - Department of Microbiology, University of Washington, Seattle, WashingtonSamuel I Miller - Department of Microbiology, University of Washington, Seattle, Washington; Department of Genome Sciences, University of Washington, Seattle, Washington; Department of Medicine, University of Washington, Seattle, WashingtonKalpaj Parekh - Department of Cardiothoracic Surgery, University of Iowa, Iowa City, IowaDavid K Meyerholz - Department of Pathology, University of Iowa, Iowa City, IowaLucas R Hoffman - Department of Pediatrics, University of Washington, Seattle, Washington; Department of Microbiology, University of Washington, Seattle, WashingtonTimothy Frana - Department of Veterinary Diagnostic & Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IowaZoe A Stewart - Department of Surgery, University of Iowa, Iowa City, IowaJohn F Engelhardt - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa. Electronic address: john-engelhardt@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.184(5), pp.1309-1322
- Publisher
- United States
- DOI
- 10.1016/j.ajpath.2014.01.035
- PMID
- 24637292
- PMCID
- PMC4005986
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Grant note
- R01 HL108902 / NHLBI NIH HHS K08 DK092284 / NIDDK NIH HHS R24 HL123482 / NHLBI NIH HHS K08 HL114725 / NHLBI NIH HHS K02 HL105543 / NHLBI NIH HHS R24 DK096518 / NIDDK NIH HHS P30 DK089507 / NIDDK NIH HHS T32 GM007337 / NIGMS NIH HHS HL108902 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS DK096518 / NIDDK NIH HHS
- Language
- English
- Date published
- 05/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Pathology; Surgery; Radiation Oncology; Cardiothoracic Surgery; Internal Medicine
- Record Identifier
- 9984025479102771
Metrics
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