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

An Erratum to this article was published on 01 May 1996

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.

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Rozmahe, R., Wilschanski, M., Matin, A. et al. Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat Genet 12, 280–287 (1996). https://doi.org/10.1038/ng0396-280

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