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

EMBO J. 1996 Mar 1;15(5):955-63.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Chlorides / metabolism
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • DNA Primers / genetics
  • Disease Models, Animal
  • Electrophysiology
  • Gene Targeting
  • Genotype
  • Humans
  • Intestinal Obstruction / genetics
  • Ion Transport / genetics
  • Meconium
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nasal Cavity / physiopathology
  • Phenotype
  • Point Mutation*

Substances

  • CFTR protein, human
  • Chlorides
  • DNA Primers
  • Cystic Fibrosis Transmembrane Conductance Regulator