Solving a mystery in Cystic Fibrosis research

February 4, 2016

Cystic Fibrosis (CF) is a life-limiting disease that is caused by mutations in the CF transmembrane conductance regulator (CFTR). People with CF are susceptible to recurring airway infections that cause progressive injury and destruction to the lungs. CF mice were generated to study the disease nearly twenty five years ago, but these models mysteriously failed to reproduce the lung disease. This spurred research into generation of new species to model the disease such as the CF pig, which developed lung disease as seen in humans. The dichotomy in animal model phenotypes provided a useful foundation for study of CF.

A team of University of Iowa researchers that included David Meyerholz, DVM, PhD (Associate Professor, Pathology) studied mice, pigs, and humans to discover that the proton pump ATP12A influenced the CF phenotype. ATP12A was expressed in humans and pigs that got CF disease, but absent in CF mice that lacked lung disease. The team discovered that in CF, ATP12A contributed to airway acidification inhibiting endogenous antimicrobial proteins in the lung and making the lungs prone to infection. In additional to identifying the reason CF mice lack lung disease, this research also identified ATP12A a candidate molecular target for future therapies for CF. These findings were published on Jan. 29 in the journal Science.

For more information please view the article posted on IowaNow.