A mouse model for the ΔF508 allele of cystic fibrosis

Abstract

The most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The ΔF508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the ΔF508 mutation into the mouse CFTR gene. Affected epithelia from homozygous ΔF508 mice lacked CFTR in the apical membrane and were Cl- impermeable. These abnormalities are the same as those observed in patients with ΔF508 and suggest that these mice have the same cellular defect. 40% of homozygous ΔF508 animals survived into adulthood and displayed several abnormalities found in human disease and in CFTR null mice. These animals should provide an excellent model to investigate pathogenesis and to examine therapies directed at correcting the ΔF508 defect.