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Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype‐phenotype correlations.
Author(s) -
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.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00432.x
Subject(s) - biology , library science , computer science
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.