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

Conference item

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: Ong, A; Harris, P; Davies, DR; Pritchard, L; Rossetti, S

• Publication status: Published
• Journal: Kidney international
• Volume: 56
• Issue: 4
• Pages: 1324-1333
• Publication date: 1999-10-01
• Event title: Forefronts in Nephrology In and Out of Control - The Regulation of Renal Cell Growth
• DOI: 10.1046/j.1523-1755.1999.00659.x
• EISSN: 1523-1755
• ISSN: 0085-2538
• Keywords: Humans; Polycystic Kidney, Autosomal Dominant; Liver; Cell Membrane; Adult; TRPP Cation Channels; Alleles; Epitopes; Kidney Tubules; Blotting, Western; Repressor Proteins; Fluorescent Antibody Technique; Proteins; Mutation; Tumor Suppressor Proteins; Gene Expression; Protein Structure, Tertiary; Antibodies, Monoclonal; Gene Deletion