title: Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype-phenotype correlations.
abstract: We have generated a mouse carrying the human G551D mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a one-step gene targeting procedure. These mutant mice show cystic fibrosis pathology but have a reduced risk of fatal intestinal blockage compared with 'null' mutants, in keeping with the reduced incidence of meconium ileus in G551D patients. The G551D mutant mice show greatly reduced CFTR-related chloride transport, displaying activity intermediate between that of cftr(mlUNC) replacement ('null') and cftr(mlHGU) insertional (residual activity) mutants and equivalent to approximately 4% of wild-type CFTR activity. The long-term survival of these animals should provide an excellent model with which to study cystic fibrosis, and they illustrate the value of mouse models carrying relevant mutations for examining genotype-phenotype correlations.
authors.affiliation: Centre for Molecular and Cellular Biology, University of Queensland, Brisbane, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Delaney
authors.forename: E W
authors.initials: EW
authors.lastname: Alton
authors.forename: S N
authors.initials: SN
authors.lastname: Smith
authors.forename: D P
authors.initials: DP
authors.lastname: Lunn
authors.forename: R
authors.initials: R
authors.lastname: Farley
authors.forename: P K
authors.initials: PK
authors.lastname: Lovelock
authors.forename: S A
authors.initials: SA
authors.lastname: Thomson
authors.forename: D A
authors.initials: DA
authors.lastname: Hume
authors.forename: D
authors.initials: D
authors.lastname: Lamb
authors.forename: D J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: J R
authors.initials: JR
authors.lastname: Dorin
authors.forename: B J
authors.initials: BJ
authors.lastname: Wainwright
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004594:Electrophysiology; D018390:Gene Targeting; D005838:Genotype; D006801:Humans; D007415:Intestinal Obstruction / Q000235:genetics; D017136:Ion Transport / Q000235:genetics; D008470:Meconium; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009296:Nasal Cavity / Q000503:physiopathology; D010641:Phenotype; D017354:Point Mutation
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator