Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype-phenotype correlations

Delaney, S.J.; Alton, E.W.; Smith, S.N.; Lunn, D.P.; Farley, R.; Lovelock, P.K.; Thomson, S.A.; Hume, D.A.; Lamb, D.; Porteous, D.J.; Dorin, J.R.; Wainwright, B.J.; Delaney, S.J; Alton, E.W; Smith, S.N; Lunn, D.P; Farley, R; Lovelock, P.K; Thomson, S.A; Hume, D.A; Lamb, D; Porteous, D.J; Dorin, J.R; Wainwright, B.J

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Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype-phenotype correlations

Delaney, S.J.; Alton, E.W.; Smith, S.N.; Lunn, D.P.; Farley, R.; Lovelock, P.K.; Thomson, S.A.; Hume, D.A.; Lamb, D.; Porteous, D.J.; Dorin, J.R.; Wainwright, B.J.

EMBO Journal 15(5): 955-963

1996

ISSN/ISBN: 0261-4189

PMID: 8605891

Document Number: 467460

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(mlUNC) replacement ('null') and cftr(mlHGU) insertional (residual activity) mutants and equivalent to approximately 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.