Genetic identification of two major modifier loci of polycystic kidney disease progression in pcy mice

J Clin Invest. 1997 Oct 15;100(8):1934-40. doi: 10.1172/JCI119724.


Unlike the uniform disease progression in inbred animals, polycystic kidney disease (PKD) progression within human families can be highly variable. This may be due to environmental or genetic factors or both. To determine if PKD severity can be influenced by modifier genes, we carried out an intercross between DBA/2-pcy/pcy and Mus m. castaneous involving 3,105 6-wk-old F2 mice. Large differences in PKD severity were observed in this cross. In addition, 23/ 800 phenotypically normal mice were pcy/pcy genotypically. These results demonstrated that PKD progression in pcy/ pcy mice is a quantitative trait that is strongly modulated by modifier genes. Whole genome quantitative trait loci mapping of 114 selected pcy/pcy mice (68 with the mild PKD and 46 with severe PKD) identified two loci, MOP1 and MOP2 that strongly modulate PKD progression. MOP1 (max LOD score = 10.3 at D4Mit111) and MOP2 (max LOD score = 13.8 at D16Mit1) accounted for 36.7 and 46.8% of the phenotypic variance, respectively. Two-factor ANOVA of the phenotypes and genotypes of all 673 pcy/pcy mice from our cross indicated that MOP1 and MOP2 alleles regulate PKD progression in a complex additive manner. Characterization of these novel modifying loci may provide additional insights into the pathogenesis of polycystic kidney diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Body Weight
  • Causality
  • Chromosome Mapping
  • Crosses, Genetic
  • Disease Progression*
  • Female
  • Genetic Variation*
  • Genotype
  • Lod Score
  • Male
  • Mice
  • Mice, Inbred DBA
  • Mice, Mutant Strains
  • Organ Size
  • Phenotype
  • Polycystic Kidney Diseases / etiology
  • Polycystic Kidney Diseases / genetics*
  • Polycystic Kidney Diseases / pathology
  • Proteins / genetics*
  • Quantitative Trait, Heritable
  • TRPP Cation Channels


  • Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein