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 cystic 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 compared with 'null' mutants, in keeping with the reduced incidence of meconium ileus in G551D patients, The G551D mutant mice show greatly reduced CFTR-related chloride transport, displaying activity intermediate between that of cftr(m1UNC) replacement ('null') and cftr(m1HGU) insertional (residual activity) mutants and equivalent to similar to 4% of wild-type CFTR activity, The long-term survival of these animals should provide an excellent model with which to study cystic fibrosis, and they illustrate the value of mouse models carrying relevant mutations for examining genotype-phenotype correlations.