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Human Molecular Genetics, 2002, Vol. 11, No. 2 125-131
© 2002 Oxford University Press

Temporal regulation of CFTR expression during ovine lung development: implications for CF gene therapy

Fiona C. Broackes-Carter, Nathalie Mouchel, Deborah Gill1, Stephen Hyde1, John Bassett2 and Ann Harris+

Paediatric Molecular Genetics, Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, Oxford OX3 9DS, UK, 1Nuffield Department of Clinical Laboratory Sciences, Oxford University, John Radcliffe Hospital, Oxford OX3 9DU, UK and 2Growth and Development Unit, Field Laboratory, Oxford University, Oxford OX2 8QJ, UK

The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a small conductance chloride ion channel that may interact directly with other channels including the epithelial sodium channel (ENaC). CFTR is known to be more abundant in the airway epithelium during the second trimester of human development than after birth. This could be a consequence of the change in function of the respiratory epithelium from chloride secretion to sodium absorption near term. Alternatively it might reflect an additional role for CFTR in the developing airway epithelium. Though the lung epithelia of CF fetuses and infants rarely show gross histological abnormalities, there is often evidence of inflammation. Our aim was to establish whether CFTR expression levels correlated with specific developmental stages or differentiated functions in the ovine fetal lung. We evaluated CFTR expression using a quantitative assay of mRNA at 14 time points through gestation and showed highest levels at the start of the second trimester followed by a gradual decline through to term. In contrast, ENaC expression increased from the start of the third trimester. These results support a role for CFTR in differentiation of the respiratory epithelium and suggest that its expression levels are not merely reflecting major changes in the sodium/chloride bulk flow close to term. These observations may have significant implications for the likely success of CF gene therapy in the postnatal lung.

+ To whom correspondence should be addressed. Fax: +44 1865 222626; Email: aharris@molbiol.ox.ac.uk


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