|Title||Cystic fibrosis in the mouse by targeted insertional mutagenesis.|
|Publication Type||Journal Article|
|Year of Publication||1992|
|Authors||Dorin JR, Dickinson P, Alton EW, Smith SN, Geddes DM, Stevenson BJ, Kimber WL, Fleming S, Clarke AR, Hooper ML|
|Date Published||1992 Sep 17|
|Keywords||Animals, Biological Transport, Chimera, Chlorine, Chromosome Mapping, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Disease Models, Animal, Female, Genes, Regulator, Genotype, Male, Membrane Potentials, Membrane Proteins, Mice, Mice, Inbred Strains, Mutagenesis, Insertional|
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.