To provide an overview of current knowledge on the structure and function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein and its role in CF disease.
To explore the different ways in which mutations in the CFTR gene can alter or abolish the function of the protein in vivo.
Summary In the 20 years since the gene responsible for cystic fibrosis (CF) was cloned, more than 1,300 mutations have been documented, which interfere with the function of the CF transmembrane conductance regulator (CFTR) protein at every stage from gene transcription to the working of the expressed protein.
Investigation of the pathogenesis of CF has led to the development of the ‘low volume’ hypothesis, whereby CFTR dysfunction leads to a depletion in airway surface liquid (ASL) and a resultant reduction in mucociliary clearance (MCC). Infection begins early in life and elicits an exaggerated and prolonged inflammatory response, which is thought to be key in the irreversible tissue destruction characteristic of CF.
- ©ERS 2008