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. 1996 Mar 1;15(5):955–963.

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

S J Delaney 1, E W Alton 1, S N Smith 1, D P Lunn 1, R Farley 1, P K Lovelock 1, S A Thomson 1, D A Hume 1, D Lamb 1, D J Porteous 1, J R Dorin 1, B J Wainwright 1
PMCID: PMC449990  PMID: 8605891

Abstract

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.

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Selected References

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