[HTML][HTML] Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue
ACM Ong, PC Harris, DR Davies, L Pritchard… - Kidney international, 1999 - Elsevier
Kidney international, 1999•Elsevier
Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue.
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 …
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 …
Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2/PKD1 cystic tissue.
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.
Elsevier