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Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1.

Mouse models for autosomal-dominant polycystic kidney disease (ADPKD), derived from homozygous targeted disruption of Pkd1 gene, generally die in utero or perinatally because of systemic defects. We introduced a loxP site and a loxP-flanked mc1-neo cassette into introns 30 and 34, respectively, of the Pkd1 locus to generate a conditional, targeted mutation. Significantly, before excision of the floxed exons and mc1-neo from the targeted locus by Cre recombinase, mice homozygous for the targeted allele appeared normal at birth but developed polycystic kidney disease with a slower progression than that of Pkd-null mice. Further, the homozygotes continued to produce low levels of full-length Pkd1-encoded protein, suggesting that slight Pkd1 expression is sufficient for renal cyst formation in ADPKD. In this viable model, up-regulation of heparin-binding epidermal growth factor-like growth factor accompanied increased epidermal growth factor receptor signaling, which may be involved in abnormal proliferation of the cyst-lining epithelia. Increased apoptosis in cyst epithelia was only observed in the later period that correlated with the cyst regression. Abnormalities in Na(+)/K(+)-ATPase, aquaporin-2, and vasopressin V2 receptor expression were also identified. This mouse model may be suitable for further studies of progression and therapeutic interventions of ADPKD.

Pubmed ID: 16400024


  • Jiang ST
  • Chiou YY
  • Wang E
  • Lin HK
  • Lin YT
  • Chi YC
  • Wang CK
  • Tang MJ
  • Li H


The American journal of pathology

Publication Data

January 9, 2006

Associated Grants


Mesh Terms

  • Animals
  • Apoptosis
  • Aquaporin 2
  • Blotting, Western
  • Disease Models, Animal
  • Epidermal Growth Factor
  • Heparin-binding EGF-like Growth Factor
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Knockout
  • Mutation
  • Polycystic Kidney Diseases
  • Proteins
  • Receptor, Epidermal Growth Factor
  • Receptors, Vasopressin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium-Potassium-Exchanging ATPase
  • TRPP Cation Channels