Correction of lethal intestinal defect in a mouse model of cystic fibrosis by human CFTR.
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). A potential animal model of CF, the CFTR-/- mouse, has had limited utility because most mice die from intestinal obstruction during the first month of life. Human CFTR (hCFTR) was expressed in CFTR-/- mice under the control of the rat intestinal fatty acid-binding protein gene promoter. The mice survived and showed functional correction of ileal goblet cell and crypt cell hyperplasia and cyclic adenosine monophosphate-stimulated chloride secretion. These results support the concept that transfer of the hCFTR gene may be a useful strategy for correcting physiologic defects in patients with CF.
Zhou
L
L
Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, OH 45229-3039.
Dey
C R
CR
Wert
S E
SE
DuVall
M D
MD
Frizzell
R A
RA
Whitsett
J A
JA
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000737:chemistry / Q000473:pathology; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004195:Disease Models, Animal; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D007421:Intestine, Small / Q000737:chemistry / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins
C505032:CFTR protein, human; D002352:Carrier Proteins; D002712:Chlorides; C107608:FABP7 protein, human; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin