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 (ΔF508), 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 CF patients with this class of mutation.
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Howard, M., Frizzell, R. & Bedwell, D. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat Med 2, 467–469 (1996). https://doi.org/10.1038/nm0496-467
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DOI: https://doi.org/10.1038/nm0496-467
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