ABCMdb

PMID: 21909392

Roth EK, Hirtz S, Duerr J, Wenning D, Eichler I, Seydewitz HH, Amaral MD, Mall MA
The K+ channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients.
PLoS One. 2011;6(8):e24445. Epub 2011 Aug 31., [PubMed]

Sentences

No. Mutations Sentence Comment

21 ABCC7 p.Gly551Asp In a recent phase 2 clinical trial in CF patients carrying the gating mutation G551D, the CFTR potentiator VX-770 [11] induced CFTR-mediated Cl2 secretion in nasal epithelia in vivo to levels of ,20% of normal [12,13]. Login to comment 46 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Thr338Ile ABCC7 p.Arg1158* ABCC7 p.Arg1158* ABCC7 p.Tyr1092* ABCC7 p.Gln39* ABCC7 p.Gln552* ABCC7 p.Gln552* ABCC7 p.Phe1052Val ABCC7 p.Gly576Ala ABCC7 p.Arg764* ABCC7 p.Ile1234Val ABCC7 p.Val232Asp ABCC7 p.Trp57* ABCC7 p.Ala561Glu ABCC7 p.Ala561Glu ABCC7 p.Ala561Glu ABCC7 p.Met1137Arg ABCC7 p.Tyr161Cys CFabsent CFresidual CFTR genotype Number of individuals CFTR genotype Number of individuals F508del/F508del 10 F508del/Y161C 1 F508del/W57X 1 F508del/V232D 1 F508del/G85E 3 F508del/R334W 2 F508del/120del23 1 F508del/T338I 1 F508del/182delT 1 F508del/I1234V 1 F508del/G542X 1 F508del/3272-26 A.G 1 F508del/A561E 1 F508del/3849+10 kb C.T 1 F508del/Y1092X 1 F508del/4005 +5727 A.G 1 F508del/N1303K 1 F508del/G576A 1 F508del/1525-1 G.A 2 N1303K/R334W 1 F508del/Q39X 1 F1052V/M1137R 1 F508del/Q552X 1 1898+3 A.G/ 1898+3 A.G 1 G85E/G85E 1 R334W/3199del6 1 Q552X/R1162X 1 R334W/X 1 A561E/A561E 2 dele2,3/X 1 R764X/1717-1 G.A 1 R1158X/2183AA.G 1 R1158X/R560T 1 doi:10.1371/journal.pone.0024445.t001 luminal and basolateral surfaces of the epithelium were perfused continuously with a solution of the following composition (mmol/ L): NaCl 145, KH2PO4 0.4, K2HPO4 1.6, D-glucose 5, MgCl2 1, Ca-gluconate 1.3, pH 7.4, at 37uC. Login to comment 79 ABCC7 p.Arg1158* (A,B) Original recordings of effects of 1-EBIO (500 mM, basolateral) on basal and carbachol-induced (CCH) transepithelial voltage (Vte) and transepithelial resistance (Rte) across rectal biopsies from a control subject (A) and a CF patient carrying two severe CFTR mutations (R1158X/2183AA.G). Login to comment 149 ABCC7 p.Arg1158* ABCC7 p.Tyr161Cys (A-C) Original recordings of effects of cAMP-mediated (IBMX/forskolin) and cholinergic (CCH) activation, and effects of 1-EBIO (500 mM, basolateral) on transepithelial voltage (Vte) and resistance (Rte) in rectal tissues from a control subject (A), a CF patient with no detectable Cl2 secretion (CFabsent; R1158X/2183AA.G) (B), and a CF patient with residual Cl2 secretion (CFresidual; F508del/Y161C), as evidence by lumen-negative Vte responses (C). Login to comment 189 ABCC7 p.Arg553* ABCC7 p.Trp1316* Hamosh A, Trapnell BC, Zeitlin PL, Montrose-Rafizadeh C, Rosenstein BJ, et al. (1991) Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis. Login to comment 199 ABCC7 p.Gly551Asp Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, et al. (2010) Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. Login to comment 203 ABCC7 p.Gly542* Du M, Liu X, Welch EM, Hirawat S, Peltz SW, et al. (2008) PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR- G542X nonsense allele in a CF mouse model. Login to comment