title: Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations.
abstract: Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (deltaF508), causes severe CF and resides on 70% of mutant chromosomes. Severe CF is also caused by premature stop mutations, which are found on 5% of CF chromosomes. Here we report that two common, disease-associated stop mutations can be suppressed by treating cells with low doses of the aminoglycoside antibiotic G-418. Aminoglycoside treatment resulted in the expression of full-length CFTR and restored its cyclic AMP-activated chloride channel activity. Another aminoglycoside, gentamicin, also promoted the expression of full-length CFTR. These results suggest that treatment with aminoglycosides may provide a means of restoring CFTR function in patients with this class of mutation.
authors.affiliation: Department of Physiology, University of Alabama at Birmingham, 35294, USA.
authors.forename: M
authors.initials: M
authors.lastname: Howard
authors.forename: R A
authors.initials: RA
authors.lastname: Frizzell
authors.forename: D M
authors.initials: DM
authors.lastname: Bedwell
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005839:Gentamicins / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D013489:Suppression, Genetic / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; C505032:CFTR protein, human; D005839:Gentamicins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C010680:antibiotic G 418