GENERATION AND CHARACTERIZATION OF A DELTA-F508 CYSTIC-FIBROSIS MOUSEMODEL

We have generated mice carrying the most common mutation in cystic fib rosis (CF), Delta F508, within the cystic fibrosis (Cftr) gene. Mutant animals show pathological and electrophysiological changes consistent with a CF phenotype. Delta F508(-/-) mice die from peritonitis and sh ow deficiencies in cAMP-activated electrogenic Cl- transport. These mi ce produce Delta F508 transcripts and show the temperature-dependent t rafficking defect first described for the human Delta F508 CFTR protei n. A functional CFTR Cl- channel not demonstrated by null CF mice or p resent at 37 degrees C was detected following incubation of epithelial cells at 27 degrees C. Thus, these mice are an accurate Delta F508 mo del and will be valuable for testing drugs aimed at overcoming the Del ta F508 trafficking defect.