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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Howard M,Frizzell RA,Bedwell DM

doi

10.1038/nm0496-467

subject

Has Abstract

pub_date

1996-04-01 00:00:00

pages

467-9

issue

4

eissn

1078-8956

issn

1546-170X

journal_volume

2

pub_type

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