Mutations of one copy of the recently described gene, PKD I, are responsible for progressive renal cyst development in type 1 autosomal dominant polycystic disease (ADPKD 1) as well as cystic and other abnormalities in liver and a variety of other organs. Its product, named poiycystin, is a large protein of unknown function and distribution. Many of the recognized cellular abnormalities in ADPKD 1 suggest that an inappropriate stage of cell differentiation lies at the center of the disease's pathogenesis. It is possible, therefore, that poiycystin is normally expressed during embryonic development and plays a role in regulating the differentiation of developing tissues. To examine this hypothesis we used polyclonal rabbit antisera against poiycystin to immunolocalize poiycystin within human fetal tissues between 20 and 36 weeks gestational age. Anti-sera were raised against synthetic peptide antigens derived from the unique C-terminal portion of the protein's predicted sequence. Normal, paraffin-embedded, fetal autopsy tissue specimens were stained by immunoperoxidase technique. Preimmune sera and immune sera pre-adsorbed with peptide antigen served as controls and were negative in all cases. At 20 weeks kidney tissue demonstrated striking staining of elongating cortical tubular epithelium but not of comma- and S-shaped bodies nor of tubular epithelial cells within medullary regions. This pattern of tubular epithelial staining persisted at 22, 26, 30 and 36 weeks with distal tubular epithelial cells also staining by 36 weeks. Liver tissue demonstrated staining of biliary epithelium and hepatocytes at 20 weeks which was present but less striking at 36 weeks. Immunostaining was also noted at all stages examined in cardiac muscle. Epithelial cells from large and small intestine were also positive. In contrast, normal human adult kidney and liver, obtained at surgery, did not show significant immunostaining. We conclude that poiycystin is normally expressed in a variety of tissues during fetal development and growth including renal tubular and biliary epithelium while it is not significantly expressed in normal adult tissue. This strengthens the hypothesis that the primary defect in ADPKD 1 is a dysregulation of cellular differentiation.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)