title: Cystic fibrosis in the mouse by targeted insertional mutagenesis.
abstract: Cystic fibrosis is a fatal genetic disorder which afflicts 50,000 people worldwide. A viable animal model would be invaluable for investigating and combating this disease. The mouse cystic fibrosis transmembrane conductance regulator gene was disrupted in embryonal stem cells using an insertional gene targeting vector. Germ-line chimaeras were derived and the offspring of heterozygous crosses studied. These homozygous mutant mice survive beyond weaning. In vivo electrophysiology demonstrates the predicted defect in chloride ion transport in these mice and can distinguish between each genotype. Histological analysis detects important hallmarks of human disease pathology, including abnormalities of the colon, lung and vas deferens. This insertional mouse mutation provides a valid model system for the development and testing of therapies for cystic fibrosis patients.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Dorin
authors.forename: P
authors.initials: P
authors.lastname: Dickinson
authors.forename: E W
authors.initials: EW
authors.lastname: Alton
authors.forename: S N
authors.initials: SN
authors.lastname: Smith
authors.forename: D M
authors.initials: DM
authors.lastname: Geddes
authors.forename: B J
authors.initials: BJ
authors.lastname: Stevenson
authors.forename: W L
authors.initials: WL
authors.lastname: Kimber
authors.forename: S
authors.initials: S
authors.lastname: Fleming
authors.forename: A R
authors.initials: AR
authors.lastname: Clarke
authors.forename: M L
authors.initials: ML
authors.lastname: Hooper
mesh_terms: D000818:Animals; D001692:Biological Transport; D002678:Chimera; D002713:Chlorine / Q000493:pharmacokinetics; D002874:Chromosome Mapping; D003550:Cystic Fibrosis / Q000235:genetics* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004195:Disease Models, Animal; D005260:Female; D005809:Genes, Regulator / Q000502:physiology; D005838:Genotype; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D016254:Mutagenesis, Insertional
chemical_list: D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002713:Chlorine