A MOUSE MODEL FOR THE DELTA-F508 ALLELE OF CYSTIC-FIBROSIS

The most common cause of cystic fibrosis is a mutation that deletes ph enylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The Delta F508 protein is misprocessed and degraded rather th an traveling to the apical membrane. We used a novel strategy to intro duce the Delta F508 mutation into the mouse CFTR gene. Affected epithe lia from homozygous Delta F508 mice lacked CFTR in the apical membrane and were Cl- impermeable. These abnormalities are the same as those o bserved in patients with Delta F508 and suggest that these mice have t he same cellular defect. 40% of homozygous Delta F508 animals survived into adulthood and displayed several abnormalities found in human dis ease and in CFTR null mice. These animals should provide an excellent model to investigate pathogenesis and to examine therapies directed at correcting the Delta F508 defect.