Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor
- 1 March 1996
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 12 (3) , 280-287
- https://doi.org/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 Cftrm1HSC/Cftrm1HSC mice should provide important insight into the heterogeneous disease presentation observed among CF patients.Keywords
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