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The use of human bronchial epithelial (HBE) cell cultures derived from the bronchi of CF patients offers the opportunity to study the effects of CFTR correctors and potentiators on CFTR function and epithelial cell biology in the native pathological environment. Cultured HBE cells deriv ...

The report of the first CF patients to receive CFTR gene therapy appeared in 1993; since then, there have been over 20 clinical trials of both viral and non-viral gene transfer agents. These have largely been single dose to either nose or lower airway and have been designed around molecular or bioelectr ...

The Nasal potential difference measurement is used to measure the voltage across the nasal epithelium, which results from transepithelial ion transport and reflects in part CFTR function. The electrophysiologic abnormality in cystic fibrosis was first described 30 years ago and co ...

Cystic fibrosis (CF) is caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR functions as an anion channel and is known to interact with a number of other cellular proteins involved in ion transport. To date more than 1,800 mutations a ...

Approximately one-third of the alleles causing genetic diseases carry premature termination codons (PTCs). Therapeutic approaches for mutations generating in-frame PTCs are aimed at promoting translational readthrough of the PTC, to enable the synthesis and expression of fu ...

In cystic fibrosis, genomic variants can result in defective processing of the CFTR precursor mRNA. Due to the complexity of the splicing process, the evaluation of their pathological effect is an important aspect both in the diagnostic field and in the study of basic regulatory mechanism. Eff ...

Extensive sequencing efforts, combined with ad hoc bioinformatics developments, have now led to the identification of 1222 distinct miRNAs in human (derived from 1368 distinct genomic loci) and of many miRNAs in other multicellular organisms. The present chapter is aimed at describing a ...

In this section, we review methods for the analysis of the CFTR gene and its transcript. First, we discuss techniques to accurately measure levels of CFTR mRNA in primary human cells; next, protocols for measuring CFTR transcripts that contain premature termination codons and for evaluating ...

The CFTR gene was identified over 20 years ago, and yet how the gene is transcriptionally regulated is not fully understood. Completion of the human genome sequence has encouraged a new generation of genomic techniques that can be used to identify and characterize the regulatory elements of the g ...

Quantification and analysis of CFTR transcripts is of crucial importance not only for cystic fibrosis (CF) diagnosis and prognosis, but also in evaluating the efficiency of various therapeutic approaches to CF, including gene therapy. Reverse transcription (RT) followed by quanti ...

Misfolding and premature degradation of F508del-CFTR is the major cause of cystic fibrosis. Components of the ubiquitin-proteasome system function on the surface of the endoplasmic reticulum to select misfolded proteins for degradation. The folding status of F508del-CFTR is mon ...

This section of Cystic Fibrosis: Diagnosis and Protocols is focussed on methods aimed at detecting expression, localization, endocytic sorting and metabolism (biogenesis and turnover), as well as interacting partners of the cystic fibrosis transmembrane conductance regula ...

Cell-free expression systems provide unique tools for understanding CFTR biogenesis because they reconstitute the cellular folding environment and are readily amenable to biochemical and pharmacological manipulation. The most common system for this purpose is rabbit reti ...

Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride secretion is critical to maintaining airway surface hydration and efficient mucociliary clearance in the upper airways. Mutations in CFTR in cystic fibrosis lead to reduced expression of funct ...

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel localized primarily at the apical surface of epithelial cells lining the airway, gut, exocrine glands, etc., where it is responsible for transepithelial salt and water transport. A growing number of pro ...

Besides its location at the plasma membrane, CFTR is present in intracellular vesicles along both the exocytic and the endocytic pathways. Immunostaining and subcellular fractionation studies of mouse kidney demonstrate that CFTR is located in endosomes of the cells lining the termi ...

The wild-type CFTR channel undergoes constitutive internalization and recycling at the plasma membrane. This process is initiated by the recognition of the Tyr- and di-Leu-based endocytic motifs of CFTR by the AP-2 adaptor complex, leading to the formation of clathrin-coated vesicles a ...

CFTR is a member of the ATP-binding cassette family of membrane proteins. This is one of the best characterised membrane protein families in terms of structure and function. CFTR operates as an ion channel, unlike nearly all other family members which are active transporters. Here, we discuss met ...

Inefficient folding of CFTR into a functional three-dimensional structure is the basic pathophysiologic mechanism leading to most cases of cystic fibrosis. Knowledge of the structure of CFTR and placement of these mutations into a structural context would provide information key f ...

Cystic fibrosis is a multi-faceted disease resulting from the dysfunction of the CFTR channel. Understanding the structural basis of channel function and the structural origin of the defect is imperative in the development of therapeutic strategies. Here, we describe molecular mode ...