Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor

Nat Genet. 1996 Mar;12(3):280-7. doi: 10.1038/ng0396-280.

Abstract

Mice that have been made deficient for the cystic fibrosis transmembrane conductance regulator (Cftr) usually die of intestinal obstruction. We have created Cftr-deficient mice and demonstrate prolonged survival among backcross and intercross progeny with different inbred strains, suggesting that modulation of disease severity is genetically determined. A genome scan showed that the major modifier locus maps near the centromere of mouse chromosome 7. Electrophysiological studies on mice with prolonged survival show that the partial rectification of Cl- and Na+ ion transport abnormalities can be explained in part by up-regulation of a calcium-activated Cl- conductance. Identification of modifier genes in our Cftr(m1HSC)/Cftr(m1HSC) mice should provide important insight into the heterogeneous disease presentation observed among CF patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chlorides / metabolism
  • Chromosome Mapping
  • Colon / pathology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / deficiency*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • DNA Primers
  • Disease Models, Animal
  • Female
  • Ileum / pathology
  • Male
  • Membrane Potentials
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutagenesis
  • Patch-Clamp Techniques
  • Survivors
  • Weight Gain

Substances

  • Chlorides
  • DNA Primers
  • Cystic Fibrosis Transmembrane Conductance Regulator