Expression of polycystin in mouse metanephros and extra-metanephric tissues

Abstract

The presence of messenger RNA for the mouse homologue of the polycystic kidney disease 1 gene (PKD1) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) methods in mouse embryo messenger RNA. A single locus for the PKD1 gene was detected on mouse chromosome 17 by fluorescent in situ hybridization. Immunoprecipitation of proteins from [35S] methionine-labeled mouse metanephric explants with an anti-polycystin antibody (Pc1) revealed high molecular weight bands, the highest being > 400 kDa. Immunoperoxidase staining of mouse embryos with Pc1 revealed expression of polycystin as early as day 8 gestation. The expression was seen in epithelial cells of the ureteric bud, in condensing blastemal cells of the developing metanephros and, subsequently, in cells of the nascent tubules. In addition, Pc1 immunoreactivity was seen in hepatocytes and biliary epithelium, cardiac and skeletal muscle, neural tissue, gut, and bronchial epithelium. In post-natal and adult mouse kidney and liver persistent slight to moderate immunoreactivity was observed. Immunofluorescent studies of cultured 13-day mouse metanephroi revealed polycystin expression in ureteric bud epithelium, early glomerular structures (that is, condensates, S-shaped and comma-shaped bodies) and in proximal and distal tubular epithelia. These data indicate that the mouse has a single gene homologous to human PKD1 on chromosome 17, and polycystin is expressed in a variety of tissues during embryonic development.

MurinePkd1 is a developmentally regulated gene from morula to adulthood: Role in tissue condensation and patterning

“…In the kidney, Pkd1 expression was found to be highly developmentally regulated, with earliest expression in uninduced mesenchyme followed by the induced epithelium and with persistence of expression in the mature glomeruli, collecting tubules, and pelvis. These findings are supported by human and murine immunolocalization studies that demonstrate PKD1 protein in condensing mesenchyme (Van Adelsberg et al, 1997) and induced epithelium of the developing nephron (Palson et al, 1996;Ward et al, 1996;Geng et al, 1997;Griffin et al, 1997;Ibraghimov-Beskrovnaya et al, 1997;Van Adelsberg et al, 1997). The temporal expression of Pkd1 in the kidney is consistent with its role as a renal developmental switch that is turned on in epithelial induction and growth, and persists at detectable expression levels in the maturation and maintenance of the normal renal tubule.…”

“…In agreement with the above model of membraneassociated protein, immunohistochemical studies have localized polycystin-1 to the plasma membrane in renal epithelial cells of fetal and adult tissue (Palson et al, 1996;Ward et al, 1996;Geng et al, 1997;Griffin et al, 1997;Ibraghimov-Beskrovnaya et al, 1997;Van Adelsberg et al, 1997). In ADPKD, however, the polycystin-1 appears to be overexpressed in the renal epithelium of most (but not all) cysts.…”

Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins

“…These domains mediate protein-protein and protein-carbohydrate interactions in other proteins, and by analogy, are likely to mediate similar interactions in polycystin-1. We and others have shown that polycystin-1 is expressed in the plasma membrane of epithelial cells (12)(13)(14)(15)(16)(17). This observation is consistent with the hypothesis that polycystin-1 might interact with an extracellular ligand or ligands.…”

Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene

“…Previous data based on immunohistochemistry and in vitro organ culture systems have suggested a role for polycystin-1 in ureteric bud growth and branching during kidney development (23,39,40). This article, however, demonstrates that polycystin-1 does not play a major role in early nephrogenesis.…”