CYSTIC-FIBROSIS MICE CARRYING THE MISSENSE MUTATION G551D REPLICATE HUMAN GENOTYPE-PHENOTYPE CORRELATIONS

We have generated a mouse carrying the human G551D mutation in the cys tic fibrosis transmembrane conductance regulator gene (CFTR) by a one- step gene targeting procedure, These mutant mice show cystic fibrosis pathology but have a reduced risk of fatal intestinal blockage compare d with 'null' mutants, in keeping with the reduced incidence of meconi um ileus in G551D patients, The G551D mutant mice show greatly reduced CFTR-related chloride transport, displaying activity intermediate bet ween that of cftr(m1UNC) replacement ('null') and cftr(m1HGU) insertio nal (residual activity) mutants and equivalent to similar to 4% of wil d-type CFTR activity, The long-term survival of these animals should p rovide an excellent model with which to study cystic fibrosis, and the y illustrate the value of mouse models carrying relevant mutations for examining genotype-phenotype correlations.