Correlation Engine 2.0
Clear Search sequence regions


  • 1 protein (1)
  • alleles (4)
  • epithelium (2)
  • expressed genes (1)
  • female (1)
  • gene (1)
  • germ line (1)
  • humans (1)
  • mice (3)
  • mice knockout (1)
  • mirnas (1)
  • mirnas (1)
  • Pkd1 (6)
  • signal (2)
  • trpp cation channels (2)
  • wolffian duct (8)
  • Sizes of these terms reflect their relevance to your search.

    Several life-threatening diseases of the kidney have their origins in mutational events that occur during embryonic development. In this study, we investigate the role of the Wolffian duct (WD), the earliest embryonic epithelial progenitor of renal tubules, in the etiology of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with a germline mutation of one of the two Pkd1 alleles. For the disease to occur, a second event that disrupts the expression of the other inherited Pkd1 allele must occur. We postulated that this secondary event can occur in the pronephric WD. Using Cre-Lox recombination, mice with WD-specific deletion of one or both Pkd1 alleles were generated. Homozygous Pkd1-targeted deletion in WD-derived tissues resulted in mice with large cystic kidneys and serologic evidence of renal failure. In contrast, heterozygous deletion of Pkd1 in the WD led to kidneys that were phenotypically indistinguishable from control in the early postnatal period. High-throughput sequencing, however, revealed underlying gene and microRNA (miRNA) changes in these heterozygous mutant kidneys that suggest a strong predisposition toward developing ADPKD. Bioinformatic analysis of this data demonstrated an upregulation of several miRNAs that have been previously associated with PKD; pathway analysis further demonstrated that the differentially expressed genes in the heterozygous mutant kidneys were overrepresented in signaling pathways associated with maintenance and function of the renal tubular epithelium. These results suggest that the WD may be an early epithelial target for the genetic or molecular signals that can lead to cyst formation in ADPKD.

    Citation

    J B Tee, A V Dnyanmote, M K Lorenzo, O R Lee, S Grisaru, M Suk, P D Acott. Pkd1-targeted mutation reveals a role for the Wolffian duct in autosomal dominant polycystic kidney disease. Journal of developmental origins of health and disease. 2020 Feb;11(1):78-85

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 31412963

    View Full Text