LOCALIZATION OF A MURINE RECESSIVE POLYCYSTIC KIDNEY-DISEASE MUTATIONAND MODIFYING LOCI THAT AFFECT DISEASE SEVERITY

We have used a novel method of chromosomal exclusion to map the recess ive mutation juvenile cystic kidney (jck) to mouse chromosome 11 using an intercross between (C57BL/6J x DBA/2J)F1jck/+ mice. The severity o f polycystic kidney disease (PKD) in the intercross progeny was signif icantly more variable than that found in the parental C57BL/6J strain, suggesting that a modifier locus or loci introduced from DBA/2J affec ts expression of jck. Two regions-one from DBA/2J on chromosome 10 and a second from CB7BL/6J on chromosome 1-are associated with inheritanc e of a more severe PKD phenotype. The finding of a highly significant association of inheritance of a C57BL/6J-related locus with disease se verity, 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 protei n products. (C) 1995 Academic Press, Inc.