Journal article
Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs
Science (American Association for the Advancement of Science), Vol.321(5897), pp.1837-1841
09/26/2008
DOI: 10.1126/science.1163600
PMCID: PMC2570747
PMID: 18818360
Abstract
Almost two decades after identification of the
CFTR
gene, we lack answers to many questions about the pathogenesis of cystic fibrosis (CF), and it remains a lethal disease. Mice with a disrupted
CFTR
gene have greatly facilitated CF studies, but they fail to develop the characteristic pancreatic, lung, intestinal, liver, and other CF manifestations. Therefore, we produced pigs with a targeted disruption of both
CFTR
alleles. These animals exhibited defective chloride transport. They also developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn patients with CF. This swine model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of treatments and preventions.
Details
- Title: Subtitle
- Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs
- Creators
- Christopher S Rogers - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242David A Stoltz - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242David K Meyerholz - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Lynda S Ostedgaard - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Tatiana Rokhlina - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Peter J Taft - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Mark P Rogan - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Alejandro A Pezzulo - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Philip H Karp - Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Omar A Itani - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Amanda C Kabel - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Christine L Wohlford-Lenane - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Greg J Davis - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Tony L Smith - Department of Surgery, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Melissa Samuel - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211David Wax - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211Clifton N Murphy - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211August Rieke - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211Kristin Whitworth - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211Aliye Uc - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Timothy D Starner - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Kim A Brogden - Department of Periodontics and Dows Institute for Dental Research College of Dentistry University of Iowa, Iowa City, Iowa 52242Joel Shilyansky - Department of Surgery, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Paul B McCray - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Joseph Zabner - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242Randall S Prather - Division of Animal Sciences University of Missouri, Columbia, Missouri 65211Michael J Welsh - Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.321(5897), pp.1837-1841
- DOI
- 10.1126/science.1163600
- PMID
- 18818360
- PMCID
- PMC2570747
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Publisher
- American Association for the Advancement of Science (AAAS)
- Grant note
- T32 HL007638-23 || HL / National Heart, Lung, and Blood Institute : NHLBI || HHMI_ / Howard Hughes Medical Institute : P30 DK054759-109004 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK P01 HL051670-15 || HL / National Heart, Lung, and Blood Institute : NHLBI P30 DK054759-10 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK K08 AI076671-01 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 09/26/2008
- Academic Unit
- Neurology; Microbiology and Immunology; Pathology; Surgery; Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Neurosurgery; Periodontics; Internal Medicine
- Record Identifier
- 9984020754802771
Metrics
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