Research LettersPulmonary disease severity in men with ΔF508 cystic fibrosis and residual chloride secretion
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Cited by (27)
Forskolin-induced swelling of intestinal organoids correlates with disease severity in adults with cystic fibrosis and homozygous F508del mutations
2020, Journal of Cystic FibrosisCitation Excerpt :In contrast, other studies suggest lack or very low function of F508del [20]. This illustrates that additional biomarkers of CFTR may help to better understand to what extent variety in CFTR function contributes to individual disease progression in people having two F508del CFTR mutations [12,13,21,22]. CFTR function can be visualized in rectal organoids upon stimulation with a cAMP-raising drug such as forskolin, which leads to CFTR channel opening and transport of ions and fluids into the organoid lumen causing rapid organoid swelling.
Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes
2015, American Journal of Human GeneticsCitation Excerpt :The strong linkage disequilibrium across the HLA region suggests that previously reported HLA allelic associations with phenotypes should be re-evaluated to consider effects of genetic variation on gene expression as a mechanistic contributor. Additionally, the GO pathways annotated to contain HLA genes are also endomembrane pathways containing genes previously associated with p.Phe508del processing, and which probably reflect genetic variation responsible for producing residual CFTR function as a result of low-level CFTR processing to the membrane in some CF individuals.43,44 The use of transformed LCLs for these expression studies provides an opportunity to rigorously explore gene expression in a well-characterized CF cohort previously utilized for GWASs.
Use of kinase inhibitors to correct ΔF508-CFTR function
2012, Molecular and Cellular ProteomicsNew clinical diagnostic procedures for cystic fibrosis in Europe
2011, Journal of Cystic FibrosisHigh-content functional screen to identify proteins that correct F508del-CFTR function
2009, Molecular and Cellular ProteomicsCitation Excerpt :Since it has been proposed that correction of even ∼10% of CFTR activity may be sufficient to restore airway epithelial function (45), the identification of even partial rescue of F508del-CFTR is significant. Moreover, since CF patients exhibiting residual Cl− channel activity have milder disease (46, 47), such partial rescue of F508del-CFTR function may have therapeutic benefits. In summary, our work here has demonstrated the development of a high-content assay to identify correctors of F508del-CFTR and the identification of several known and novel proteins that when co-expressed with F508del-CFTR lead to rescue of its trafficking and functional defects.
Airway ion transport impacts on disease presentation and severity in cystic fibrosis
2008, Clinical Biochemistry