Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations

Academic Article

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 amino-glycoside, 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.
  • Published In

  • Nature Medicine  Journal
  • Digital Object Identifier (doi)

    Author List

  • Howard M; Frizzell RA; Bedwell DM
  • Start Page

  • 467
  • End Page

  • 469
  • Volume

  • 2
  • Issue

  • 4