title: Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic.
abstract: Numerous mouse models of polycystic kidney disease (PKD) have been described. All of these diseases are transmitted as single recessive traits and in most, the phenotypic severity is influenced by the genetic background. However, based on their genetic map positions, none of these loci appears to be allelic and none are candidate modifier loci for any other mouse PKD mutation. Previously, we have described the mouse bpk mutation, a model that closely resembles human autosomal recessive polycystic kidney disease. We now report that the bpk mutation maps to a 1.6 CM interval on mouse Chromosome 10, and that the renal cystic disease severity in our intersubspecific intercross progeny is influenced by the genetic background. Interestingly, bpk co-localizes with jcpk, a phenotypically-distinct PKD mutation, and complementation testing indicates that the bpk and jcpk mutations are allelic. These data imply that distinct PKD phenotypes can result from different mutations within a single gene. In addition, based on its map position, the bpk locus is a candidate genetic modifier for jck, a third phenotypically-distinct PKD mutation.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Guay-Woodford
authors.forename: E C
authors.initials: EC
authors.lastname: Bryda
authors.forename: B
authors.initials: B
authors.lastname: Christine
authors.forename: J R
authors.initials: JR
authors.lastname: Lindsey
authors.forename: W R
authors.initials: WR
authors.lastname: Collier
authors.forename: E D
authors.initials: ED
authors.lastname: Avner
authors.forename: P
authors.initials: P
authors.lastname: D'Eustachio
authors.forename: L
authors.initials: L
authors.lastname: Flaherty
mesh_terms: D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D005816:Genetic Complementation Test; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000473:pathology; D011995:Recombination, Genetic