Track topics on Twitter Track topics that are important to you
Cross-species comparative studies have highlighted differences between human and mouse cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial Cl channel defective in cystic fibrosis (CF). Here, we compare the impact of the most common CF mutation F508del on the function of human and mouse CFTR heterologously expressed in mammalian cells and their response to CFTR modulators using the iodide efflux and patch-clamp techniques. Once delivered to the plasma membrane, human F508del-CFTR exhibited a severe gating defect characterized by infrequent channel openings and was thermally unstable, deactivating within minutes at 37 °C. By contrast, the F508del mutation was without effect on the gating pattern of mouse CFTR and channel activity demonstrated thermostability at 37 °C. Strikingly, at all concentrations tested, the clinically-approved CFTR potentiator ivacaftor was without effect on the mouse F508del-CFTR Cl channel. Moreover, eight CFTR potentiators, including ivacaftor, failed to generate CFTR-mediated iodide efflux from CHO cells expressing mouse F508del-CFTR. However, they all produced CFTR-mediated iodide efflux with human F508del-CFTR-expressing CHO cells, while fifteen CFTR correctors rescued the plasma membrane expression of both human and mouse F508del-CFTR. Interestingly, the CFTR potentiator genistein enhanced CFTR-mediated iodide efflux from CHO cells expressing either human or mouse F508del-CFTR, whereas it only potentiated human F508del-CFTR Cl channels in cell-free membrane patches, suggesting that its action on mouse F508del-CFTR is indirect. Thus, the F508del mutation has distinct effects on human and mouse CFTR Cl channels.
This article was published in the following journal.
Name: American journal of physiology. Lung cellular and molecular physiology
Cystic fibrosis (CF) genotyping has garnered increased attention since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 led to the identification of over 17...
The advent of precision treatment for cystic fibrosis (CF) using small-molecule therapeutics has created a need to estimate potential clinical improvements attributable to increases in cystic fibrosis...
Cystic fibrosis (CF; OMIM 219700) is caused by variations in the cystic fibrosis transmembrane conductance regulator gene. CF-related liver disease (CFLD) affects approximately one-third of patients w...
Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that improves pulmonary function in cystic fibrosis (CF) patients with at least 1 copy of the G551D CFTR mutation....
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. Many CF patients have asthma-like symptoms and airway hyperr...
OBJECTIVES: Evaluate the efficacy and safety of lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator gene to nasal epithelium in patients with cystic f...
This is a pilot study. The purpose of the study is to facilitate the development of a new biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) function using rectal tis...
Cystic fibrosis is a genetic disease caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR). The purpose of the study is to investigate the effects of miglust...
In order to further enable physiopathology studies, the aim of this project is to validate an in vitro model of cystic fibrosis created using induced pluripotent stemcell (iPS) differentia...
Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The encoded protein, CFTR, is an epithelial chloride ion channel respon...
A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.
A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
A forkhead box transcription factor that is a major target of INSULIN signaling and regulator of metabolic homeostasis in response to OXIDATIVE STRESS. It binds to the insulin RESPONSE ELEMENT (IRE) and the related Daf-16 family binding element (DBE). Its activity is suppressed by insulin and it also regulates OSTEOBLAST proliferation, controls bone mass, and skeletal regulation of GLUCOSE metabolism. It promotes GLUCONEOGENESIS in HEPATOCYTES and regulates gene expression in ADIPOSE TISSUE. It is also an important CELL DEATH regulator. Chromosomal aberrations involving the FOXO1 gene occur in RHABDOMYOSARCOMA.
Affecting over 8,500 people in the UK, Cystic Fibrosis (CF) is one of the UK's most common life-threatening inherited diseases. Around half of the CF population can expect to live over 38 years, although improvements in treatments mean a baby born ...
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza, Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...