What is Cystic Fibrosis?

Cystic fibrosis (CF) is characterised by abnormal epithelial ion transport in the apical membrane of most secretory cells. This leads to altered epithelial mucus secretion in the gastrointestinal tract, reproductive tract, liver, pancreas and most severely in the pulmonary epithelium.



History of Cystic Fibrosis

Cystic fibrosis (CF) was first recognised over 400 years ago in Germany and is the most common autosomal recessive disorder in Caucasians (Berkow et al., 1998). It is a hereditary disease that causes certain glands to produce abnormal secretions, the most important of which affect the digestive tract, the pancreas and the airway epithelia (Hodson & Geddes, 1995).



Discovery of the CFTR Gene

In the early 1980s a number of novel molecular tools were applied to CF to try to map the genomic location of the gene responsible for CF (Mayo, B. J. et al., 1980). With the application of restriction fragment length polymorphism (RFLP) analysis (Kan, Y. W. & Dozy, A. M., 1978) the CF locus was tightly mapped to human chromosome 7q31 (right) (Knowlton, R. G. et al., 1985; White, R. et al., 1985;Wainwright, B. et al., 1986).



What causes Cystic Fibrosis?

CF affects the epithelial lining of many organs but most significantly the airway epithelium of the lung. Mutations in the CFTR gene lead to the production of a misfolded CFTR protein which cannot be transported properly to the cell surface or is non-functional when it does get there.



CFTR Protein Structure

The cystic fibrosis transmembrane conductance regulator (CFTR) is a 1480 amino acid membrane bound glycoprotein with a molecular mass of 170,000. It is a member of the ATP binding cassette (ABC) superfamily of proteins which includes several clinically important proteins such as P-glycoprotein (P-gp), multidrug resistance associated protein and the TAP transporters. The protein is comprised of two, six span membrane bound regions each connected to a nuclear binding factor which binds ATP. Betwee




Schematic diagram of the large human airways.


Proposed 3D model of the CFTR protein.