title: A mouse model for the delta F508 allele of cystic fibrosis.
abstract: The most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The delta F508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the delta F508 mutation into the mouse CFTR gene. Affected epithelia from homozygous delta F508 mice lacked CFTR in the apical membrane and were Cl-impermeable. These abnormalities are the same as those observed in patients with delta F508 and suggest that these mice have the same cellular defect. 40% of homozygous delta F508 animals survived into adulthood and displayed several abnormalities found in human disease and in CFTR null mice. These animals should provide an excellent model to investigate pathogenesis and to examine therapies directed at correcting the delta F508 defect.
authors.affiliation: Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Zeiher
authors.forename: E
authors.initials: E
authors.lastname: Eichwald
authors.forename: J
authors.initials: J
authors.lastname: Zabner
authors.forename: J J
authors.initials: JJ
authors.lastname: Smith
authors.forename: A P
authors.initials: AP
authors.lastname: Puga
authors.forename: P B
authors.initials: PB
authors.lastname: McCray
authors.forename: M R
authors.initials: MR
authors.lastname: Capecchi
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
authors.forename: K R
authors.initials: KR
authors.lastname: Thomas
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004064:Digestive System / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004573:Electrolytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010183:Pancreatic Ducts / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
chemical_list: C505032:CFTR protein, human; D004573:Electrolytes; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator