Polycystic Kidney Disease

 

Student projects

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Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic disease primarily affecting the kidneys. The formation of a large number of fluid-filled cysts in both kidneys together with interstitial fibrosis usually cause chronic renal failure in 50% of patients by the age of 60 years .  Frequently occurring extra-renal manifestations are hypertension, cardio-valvular abnormalities, cysts in other organs such as liver and pancreas, and the occurrence of cerebral aneurysms

ADPKD has an incidence of 1 in 1000 in Caucasians and can be caused by a mutation in at least three different genes. Mutations in the PKD1-gene cause ADPKD in approximately 85% of ADPKD-families, whereas mutations in the PKD2-gene are responsible for the disease in most of the remaining 15% of families .

Polycystin-1 and polycystin-2:   The polycystic kidney disease 1 (PKD1) gene encodes an integral membrane glycoprotein, polycystin-1, containing a subset of structural motifs that may be involved in protein interactions. These motifs, supported by immunostaining and precipitation experiments, suggest that polycystin-1 functions in cell-cell and/or cell-matrix interactions. The carboxy terminus of polycystin-1 has been shown to interact, via an a-helical coiled-coil domain, with a region in the carboxy terminus of polycystin-2 . This protein shows homology to the pore forming units of a number of cation channels. Measurable non-selective cation channel activity of both  polycystin-2 alone, and co-assembled with polycystin-1 has been demonstrated.  Thus, polycystin-1 and 2 seem to function in various cellular processes. The interaction between these proteins is probably needed for crucial cellular processes involved in the maintenance of the (renal) epithelial architecture. Expression of both proteins has been  detected in several nephronic segments but the exact role of these proteins in cyst formation and in other disease manifestations remains to be determined .

The main aims of our research are the characterization and  functional analysis of genes involved in the pathophysiology of  Polycystic Kidney Disease using genetic, cellular and transgenic mouse model approaches.

 

Project topics for students Biomedical Sciences, Medicine, Biology, Chemistry and HLO-stagaires.

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