title: Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue.
abstract: 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.
authors.affiliation: MRC Molecular Haematology Unit, Institute of Molecular Medicine, University of Oxford, United Kingdom. a.ong@Sheffield.ac.uk
authors.forename: A C
authors.initials: AC
authors.lastname: Ong
authors.forename: P C
authors.initials: PC
authors.lastname: Harris
authors.forename: D R
authors.initials: DR
authors.lastname: Davies
authors.forename: L
authors.initials: L
authors.lastname: Pritchard
authors.forename: S
authors.initials: S
authors.lastname: Rossetti
authors.forename: S
authors.initials: S
authors.lastname: Biddolph
authors.forename: D J
authors.initials: DJ
authors.lastname: Vaux
authors.forename: N
authors.initials: N
authors.lastname: Migone
authors.forename: C J
authors.initials: CJ
authors.lastname: Ward
mesh_terms: D000328:Adult; D000483:Alleles; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002462:Cell Membrane / Q000737:chemistry; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007684:Kidney Tubules / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D050396:TRPP Cation Channels; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D011506:Proteins; D012097:Repressor Proteins; D050396:TRPP Cation Channels; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C000624653:TSC2 protein, human