Why don’t mice with cystic fibrosis (CF) gene mutations develop the life-threatening lung disease that affects most people with CF?
University of Iowa researchers working on this long-standing scientific puzzle now have an answer, which identifies a proton pump as a potential target for new CF therapies. The results were published Jan. 29 in Science.
In people, pigs, and mice with CF, loss of the cystic fibrosis transmembrane conductance regulator (CFTR) stops the flow of bicarbonate, a base. When that happens in people and pigs, the liquid that covers the surfaces of the tracheal and bronchial passages becomes more acidic, which impairs airway defenses against infection. But in mice, the airway liquid does not become more acidic, and the mice are not prone to infection.
The critical difference is a proton pump called ATP12A that secretes acid into the airways of people and pigs but is missing in the mice.
“This discovery helps us understand the cause of lung disease in people with CF. It may also identify ATP12A as a new therapeutic target,” says Viral Shah, a student in the Medical Scientist Training Program at the UI Carver College of Medicine. “We wonder if blocking ATP12A in people with CF could halt the progression of lung disease.”