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- Title
Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue.
- Authors
Ong, Albert C.M.; Harris, Peter C.; Davies, David R.; Pritchard, Lynn; Rossetti, Sandro; Biddolph, Simon; Vaux, David J.T.; Migone, Nicola; Ward, Christopher J.; Ong, A C; Harris, P C; Davies, D R; Pritchard, L; Rossetti, S; Biddolph, S; Vaux, D J; Migone, N; Ward, C J
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
POLYCYSTIC kidney disease; GENETIC mutation; ALLELES; ANTIGENS; CARRIER proteins; CELL membranes; COMPARATIVE studies; FLUORESCENT antibody technique; GENE expression; KIDNEY tubules; LIVER; RESEARCH methodology; MEDICAL cooperation; MONOCLONAL antibodies; PROTEINS; RESEARCH; WESTERN immunoblotting; EVALUATION research
- Publication
Kidney International, 1999, Vol 56, Issue 4, p1324
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1046/j.1523-1755.1999.00659.x