Localization of a murine recessive polycystic kidney disease mutation and modifying loci that affect disease severity.
We have used a novel method of chromosomal exclusion to map the recessive mutation juvenile cystic kidney (jck) to mouse chromosome 11 using an intercross between (C57BL/6J x DBA/2J) F1jck/ + mice. The severity of polycystic kidney disease (PKD) in the intercross progeny was significantly more variable than that found in the parental C57BL/6J strain, suggesting that a modifier locus or loci introduced from DBA/2J affects expression of jck. Two regions--one from DBA/2J on chromosome 10 and a second from C57BL/6J on chromosome 1--are associated with inheritance of a more severe PKD phenotype. The finding of a highly significant association of inheritance of a C57BL/6J-related locus with disease severity, with a maximal QTL analysis lod score of 16.8, was unexpected; this result suggests that inheritance of both this locus and at least one DBA/2J locus results in the more severe phenotype, presumably as a consequence of a direct or indirect interaction between their protein products.
Iakoubova
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Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Dushkin
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Beier
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D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D003433:Crosses, Genetic; D004276:DNA, Satellite / Q000235:genetics; D008040:Genetic Linkage; D005819:Genetic Markers; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D009154:Mutation; D009929:Organ Size; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics*
D004276:DNA, Satellite; D005819:Genetic Markers