title: Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs.
abstract: Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Rogers
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.forename: Lynda S
authors.initials: LS
authors.lastname: Ostedgaard
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rokhlina
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Taft
authors.forename: Mark P
authors.initials: MP
authors.lastname: Rogan
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Pezzulo
authors.forename: Philip H
authors.initials: PH
authors.lastname: Karp
authors.forename: Omar A
authors.initials: OA
authors.lastname: Itani
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Kabel
authors.forename: Christine L
authors.initials: CL
authors.lastname: Wohlford-Lenane
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Davis
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hanfland
authors.forename: Tony L
authors.initials: TL
authors.lastname: Smith
authors.forename: Melissa
authors.initials: M
authors.lastname: Samuel
authors.forename: David
authors.initials: D
authors.lastname: Wax
authors.forename: Clifton N
authors.initials: CN
authors.lastname: Murphy
authors.forename: August
authors.initials: A
authors.lastname: Rieke
authors.forename: Kristin
authors.initials: K
authors.lastname: Whitworth
authors.forename: Aliye
authors.initials: A
authors.lastname: Uc
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Starner
authors.forename: Kim A
authors.initials: KA
authors.lastname: Brogden
authors.forename: Joel
authors.initials: J
authors.lastname: Shilyansky
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
authors.forename: Randall S
authors.initials: RS
authors.lastname: Prather
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005704:Gallbladder / Q000473:pathology; D045823:Ileus / Q000473:pathology / Q000503:physiopathology; D007422:Intestines / Q000473:pathology; D017136:Ion Transport; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D046790:Pancreas, Exocrine / Q000473:pathology; D011995:Recombination, Genetic; D013552:Swine
chemical_list: D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator