ABCMdb

PMID: 15510065

Kerem E
Pharmacologic therapy for stop mutations: how much CFTR activity is enough?
Curr Opin Pulm Med. 2004 Nov;10(6):547-52., [PubMed]

Sentences

No. Mutations Sentence Comment

51 ABCC7 p.Trp1282* In the Ashkenazi Jewish population, the W1282X mutation is the most common CF-causing mutation, and together with other nonsense mutations, accounts for 64% of all CFTR alleles [8,9]. Login to comment 82 ABCC7 p.Arg553* ABCC7 p.Gly542* Howard et al. [21] demonstrated in Hela cells transfected with plasmid vector carrying the CFTR nonsense mutations G542X and R553X that aminoglycosides caused a dose-dependent increase in CFTR expression. Login to comment 83 ABCC7 p.Trp1282* Subsequently, the same group has shown that the functional CFTR was restored to the apical membrane and the relative level of mRNA increased in bronchial cell line IB3-1 expressing the W1282X mutation. Login to comment 86 ABCC7 p.Gly542* Zsembery et al. [23] isolated cholangiocytes from the liver of a patient carrying the G542X mutation, and incubated them with gentamicin, and they exhibited cAMP activated chloride transport. Login to comment 89 ABCC7 p.Gly542* Immunofluorescence staining of intestinal tissues from Cftr-/- mouse carrying a human CFTR-G542X transgene revealed that gentamicin treatment resulted in the appearance of human CFTR protein at the apical surface of the glands of treated mice. Login to comment 92 ABCC7 p.Gly542* When taken together, these results indicate that gentamicin, and to a lesser extent tobramycin, can restore the synthesis of functional human CFTR protein by suppressing the human CFTR-G542X premature stop mutation in vivo. Login to comment 117 ABCC7 p.Trp1282* In this double-blind, crossover, placebo-controlled trial [27••] as well as in our previous pilot study [25], all patients in the stop mutation group carried at least one W1282X allele. Login to comment 133 ABCC7 p.Arg553* ABCC7 p.Gly542* Quantification studies have shown that after aminoglycoside incubation, the amount of full-length CFTR produced is as much as 25% (in the R553X mutation) to 35% (in the G542X mutation) of that observed in cells transfected with a wild-type CFTR complementary DNA [18,22]. Login to comment