A CFTR potentiator in patients with Cystic Fibrosis and the G551D Mutation

Ramsey, Bonnie W., Davies, Jane, McElvaney, N. Gerard, Tullis, Elizabeth, Bell, Scott C., Drevinek, Pavel, Griese, Matthias, McKone, Edward F., Wainwright, Claire E., Konstan, Michael W., Moss, Richard, Ratjen, Felix, Sermet-Gaudelus, Isabelle, Rowe, Steven M., Dong, Qunming, Rodriguez, Sally, Yen, Karl, Ordonez, Claudia and Elborn, J. Stuart (2011) A CFTR potentiator in patients with Cystic Fibrosis and the G551D Mutation. New England Journal of Medicine, 365 18: 1663-1672. doi:10.1056/NEJMoa1105185

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Author Ramsey, Bonnie W.
Davies, Jane
McElvaney, N. Gerard
Tullis, Elizabeth
Bell, Scott C.
Drevinek, Pavel
Griese, Matthias
McKone, Edward F.
Wainwright, Claire E.
Konstan, Michael W.
Moss, Richard
Ratjen, Felix
Sermet-Gaudelus, Isabelle
Rowe, Steven M.
Dong, Qunming
Rodriguez, Sally
Yen, Karl
Ordonez, Claudia
Elborn, J. Stuart
Title A CFTR potentiator in patients with Cystic Fibrosis and the G551D Mutation
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
Publication date 2011-11-01
Sub-type Article (original research)
DOI 10.1056/NEJMoa1105185
Open Access Status File (Publisher version)
Volume 365
Issue 18
Start page 1663
End page 1672
Total pages 10
Place of publication Boston, MA, U.S.A.
Publisher Massachusetts Medical Society
Language eng
Abstract Trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) is central to its function, with the most common mutation, deltaF508, resulting in abnormal processing and trafficking. Therefore, there is a significant need to develop tools, which enable the trafficking of CFTR to be studied in vitro and in vivo. In previous studies it has been demonstrated that fusion of the green fluorescent protein (GFP) to the N-terminus of CFTR does lead to functional expression of CFTR chloride channels in epithelial cell lines. The aim of the present study was to examine whether it is possible to express GFP-tagged CFTR as a transgene in colonic and airway epithelial cells of cystic fibrosis (CF) mice and to correct the CF defect. Using the epithelial-specific human cytokeratin promoter K18, we generated bitransgenic mice cftr(G551D/G551) K18-GFP-CFTR(+/-), designated GFP mice. Transcripts for GFP-CFTR could be detected in bitransgenic mice by use of RT-PCR techniques. Expression of GFP-CFTR protein was detected specifically in the colonic epithelium by both direct GFP fluorescence and the use of an anti-GFP antibody. Ussing chamber studies showed that the ion transport defect in colon and airways observed in cftr(G551D/G551D) mice was partially corrected in the bitransgenic animals. Thus, K18-GFP-CFTR is functionally expressed in transgenic mice, which will be a valuable tool in studies on CFTR synthesis, processing and ion transport in native epithelial tissues.
Keyword Randomized Controlled-Trial
Pseudomonas-Aeruginosa
Pulmonary-Function
Identification
Questionnaire
Azithromycin
Mechanisms
Guidelines
Health
Vx-770
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes VX08 770 102 Study Grp

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
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