Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs.
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.
Rogers
Christopher S
CS
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Stoltz
David A
DA
Meyerholz
David K
DK
Ostedgaard
Lynda S
LS
Rokhlina
Tatiana
T
Taft
Peter J
PJ
Rogan
Mark P
MP
Pezzulo
Alejandro A
AA
Karp
Philip H
PH
Itani
Omar A
OA
Kabel
Amanda C
AC
Wohlford-Lenane
Christine L
CL
Davis
Greg J
GJ
Hanfland
Robert A
RA
Smith
Tony L
TL
Samuel
Melissa
M
Wax
David
D
Murphy
Clifton N
CN
Rieke
August
A
Whitworth
Kristin
K
Uc
Aliye
A
Starner
Timothy D
TD
Brogden
Kim A
KA
Shilyansky
Joel
J
McCray
Paul B
PB
Zabner
Joseph
J
Prather
Randall S
RS
Welsh
Michael J
MJ
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
D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator