Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets
| Autor: | Nicholas W. Keiser, Joann M. Kinyon, Thomas J. Lynch, Weihong Zhou, John F. Engelhardt, Xingshen Sun, Yaling Yi, Scott R. Tyler, J. Adam Goeken, Yulong Zhang, Yi Song, Timothy S. Frana, Xiaoming Liu, Lucas R. Hoffman, Kalpaj R. Parekh, Mitchell J. Brittnacher, Weiliang Xie, Alicia K. Olivier, Hongshu Sui, Bo Liang, David K. Meyerholz, Xiaoyan Wang, Samuel I. Miller, Danielle Fligg, Kyle R. Hager, John T. Fisher, Zoe A. Stewart, Paul M. Kaminsky, Ziying Yan, Christopher E. Pope, Hillary S. Hayden, Matthew C. Radey |
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| Rok vydání: | 2014 |
| Předmět: |
Aging
medicine.medical_specialty Pathology Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Gastroenterology Cystic fibrosis Pathology and Forensic Medicine Gene Knockout Techniques Atrophy Fibrosis Internal medicine medicine Animals Humans Gastrointestinal tract Bacteria biology Biliary hyperplasia Gallbladder Ferrets Regular Article Gastrointestinal pathology medicine.disease Cystic fibrosis transmembrane conductance regulator 3. Good health Gastrointestinal Tract Mucus medicine.anatomical_structure Organ Specificity biology.protein |
| Zdroj: | The American Journal of Pathology. 184:1309-1322 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2014.01.035 |
| Popis: | 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 ( |
| Databáze: | OpenAIRE |
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