title: Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor.
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.
authors.affiliation: Department of Molecular Genetics, The University of Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Rozmahel
authors.forename: M
authors.initials: M
authors.lastname: Wilschanski
authors.forename: A
authors.initials: A
authors.lastname: Matin
authors.forename: S
authors.initials: S
authors.lastname: Plyte
authors.forename: M
authors.initials: M
authors.lastname: Oliver
authors.forename: W
authors.initials: W
authors.lastname: Auerbach
authors.forename: A
authors.initials: A
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Forstner
authors.forename: P
authors.initials: P
authors.lastname: Durie
authors.forename: J
authors.initials: J
authors.lastname: Nadeau
authors.forename: C
authors.initials: C
authors.lastname: Bear
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D002874:Chromosome Mapping; D003106:Colon / Q000473:pathology; D003550:Cystic Fibrosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency* / Q000235:genetics; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D007082:Ileum / Q000473:pathology; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016296:Mutagenesis; D018408:Patch-Clamp Techniques; D017741:Survivors; D015430:Weight Gain
chemical_list: D002712:Chlorides; D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator