Cystic fibrosis in the mouse by targeted insertional mutagenesis

Cystic flbrosis 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 flbrosis transmembrane conductance regulator gene was disrupted in embryonal stem cells using an insertional ge...

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Bibliographic Details
Published in:Nature (London) 1992-09, Vol.359 (6392), p.211-215
Main Authors: Dorin, Julia R, Dickinson, Paul, Alton, Eric W. F. W, Smith, Stephen N, Geddes, Duncan M, Stevenson, Barbara J, Kimber, Wendy L, Fleming, Stewart, Clarke, Alan R, Hooper, Martin L, Anderson, Louise, Beddington, Rosa S. P, Porteous, David J
Format: Article
Language:English
Subjects:
Animal models
Animals
Biological and medical sciences
Biological Transport
Chimera
Chlorine - pharmacokinetics
Chromosome Mapping
Cystic fibrosis
Cystic Fibrosis - genetics
Cystic Fibrosis - pathology
Cystic Fibrosis Transmembrane Conductance Regulator
Disease Models, Animal
Female
Gastroenterology. Liver. Pancreas. Abdomen
Genes, Regulator - physiology
Genotype
Humanities and Social Sciences
Ion transport
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical research
Medical sciences
Membrane Potentials
Membrane Proteins - genetics
Mice
Mice, Inbred Strains
multidisciplinary
Mutagenesis, Insertional
Mutation
Offspring
Other diseases. Semiology
Rodents
Science
Science (multidisciplinary)
Stem cells
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Summary:Cystic flbrosis 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 flbrosis 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/359211a0