Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue

Kidney Int. 1999 Oct;56(4):1324-33. doi: 10.1046/j.1523-1755.1999.00659.x.


Background: The mutational mechanism responsible for cyst formation in polycystic kidney disease 1 gene (PKD1) remains controversial, with data indicating a two-hit mechanism, but also evidence of polycystin-1 expression in cystic tissue.

Methods: To investigate this apparent paradox, we analyzed polycystin-1 expression in cystic renal or liver tissue from 10 patients with truncating PKD1 mutations (including one early-onset case) and 2 patients with severe disease associated with contiguous deletions of TSC2 and PKD1, using monoclonal antibodies (mAbs) to both extreme N-(7e12) and C-terminal (PKS-A) regions of the protein. Truncation of the C-terminal epitope from the putative mutant proteins in each case allowed exclusive assessment of the nontruncated protein with PKS-A.

Results: In adult PKD1 tissue, the majority of cysts (approximately 80%) showed polycystin-1 expression, although staining was absent in a variable but significant minority (approximately 20%), in spite of the normal expression of marker proteins. Unlike adult PKD1, however, negative cysts were rarely found in infantile PKD1 or TSC2/PKD1 deletion cases.

Conclusions: If a two-hit mutational mechanism is operational, these results suggest that the majority of somatic mutations in adult PKD1 are likely to be missense changes. The low level of polycystin-1-negative cysts in the three "early-onset" cases, however, suggests that a somatic PKD1 mutation may not always be required for cyst formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antibodies, Monoclonal
  • Blotting, Western
  • Cell Membrane / chemistry
  • Epitopes / immunology
  • Fluorescent Antibody Technique
  • Gene Deletion
  • Gene Expression
  • Humans
  • Kidney Tubules / chemistry
  • Kidney Tubules / metabolism*
  • Liver / metabolism
  • Mutation
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / immunology
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / immunology
  • TRPP Cation Channels
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins


  • Antibodies, Monoclonal
  • Epitopes
  • Proteins
  • Repressor Proteins
  • TRPP Cation Channels
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • polycystic kidney disease 1 protein