ABCMdb

PMID: 22672057

Keeling KM, Wang D, Conard SE, Bedwell DM
Suppression of premature termination codons as a therapeutic approach.
Crit Rev Biochem Mol Biol. 2012 Sep;47(5):444-63. doi: 10.3109/10409238.2012.694846. Epub 2012 Jun 7., [PubMed]

Sentences

No. Mutations Sentence Comment

218 ABCC7 p.Gly542* The G542X mutation, found in 2% of Caucasian CF patients, is the most common CFTR nonsense mutation. Login to comment 224 ABCC7 p.Gly551Asp The G551D mutation, a CFTR gating mutant found in approximately 4% of CF patients, is an example of this mutation class. Class IV is made up of mutations that allow correct CFTR localization and activation by cAMP, but with reduced chloride conductance. Login to comment 234 ABCC7 p.Gly542* Studies to examine suppression of a CFTR nonsense mutation utilized a transgenic mouse that carried a human CFTR cDNA containing the G542X nonsense mutation. Login to comment 236 ABCC7 p.Gly542* The CFTR-G542X transgene was then crossed into a Cftrtm1Cam knockout mouse, resulting in a mouse that was suitable to evaluate the ability of suppression therapy to restore CFTR protein function (Du et al., 2002). Login to comment 244 ABCC7 p.Gly542* In summary, a number of different drugs were found to suppress the common G542X mutation in a transgenic CF mouse model. Login to comment 395 ABCC7 p.Gly551Asp VX-809 was developed for CF patients with the Class II mutation F508del that affects CFTR trafficking (Van Goor et al., 2011), and VX-770 (Kalydeco&#ae; ) was developed for the Class III mutation G551D that produces correctly localized CFTR, but causes channel gating defects (Van Goor et al., 2009). Login to comment 518 ABCC7 p.Gly542* Aminoglycoside suppression of a premature stop mutation in a Cftr-/- mouse carrying a human CFTR-G542X transgene. Login to comment 521 ABCC7 p.Gly542* Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model. Login to comment 524 ABCC7 p.Gly542* PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Login to comment 531 ABCC7 p.Gly542* Poly-l-aspartic acid enhances and prolongs gentamicin-mediated suppression of the CFTR-G542X mutation in a cystic fibrosis mouse model. Login to comment