It's been more than 20 years since scientists first discovered the gene that causes cystic fibrosis (CF), yet questions about how the mutated gene causes disease remain unanswered.
Using a newly created pig model that genetically replicates the most common form of cystic fibrosis, University of Iowa researchers have now shown that the CF protein is "misprocessed" in the pigs and does not end up in the correct cellular location. This glitch leads to disease symptoms, including gastrointestinal abnormalities and lung disease in the pigs, which mimic CF in humans. The findings are published in the March 16 issue of the journal Science Translational Medicine.
The findings match earlier laboratory experiments that suggested the gene mutation disrupts the process whereby the CF protein is folded into its correct shape and shipped to the membranes of cells that line the airways and other organs.
When it is correctly located at the cell membrane, this protein -- called cystic fibrosis transmembrane conductance regulator (CFTR) -- forms a channel to allow chloride ions to move in and out of cells. This ion movement is a critical component of the system that maintains salt and water balance across cell membranes in the lung as well as other organs and supports normal membrane function including eradicating bacteria from cell surfaces.
The new study shows that in pigs, the CFTR protein behaves the same way in a living animal as it does in experimental cell systems, suggesting that these experimental systems are useful for learning about the CFTR protein's properties. The cell systems and the new pig model may also be helpful in testing therapies designed to increase the amount of protein that gets to the cell membrane, or boost the activity of the protein that is located at the membrane.
"Instead of just trying to treat the symptoms of CF, current research is moving toward therapies that target mutations in the CFT
|Contact: Jennifer Brown|
University of Iowa Health Care