ProjectZilienanomalien als Ursache renaler Dysfunktion in GRK4-assoziierter Hypertonie

Basic data

Zilienanomalien als Ursache renaler Dysfunktion in GRK4-assoziierter Hypertonie
01/01/2020 to 31/01/2021
Abstract / short description:
Up to 25% of the Western population develops a high blood pressure that correlates with increased sensitivity to sodium. The majority of these hypertensive patients carry genetic variants of G protein-coupled receptor kinase 4 (GRK4) with an elevated potency in the regulation of dopaminergic receptors. Dopaminergic receptors are crucial for the modulation of renal sodium transport into the proximal tubule and thus blood pressure. In the presence of GRK4 SNPs dopaminergic receptors are uncoupled rendering natriuresis impaired and blood pressure increased. Here, we propose that GRK4 may control kidney function also on the level of cilia. We found that loss of GRK4 results in cilia anomalies in fibroblasts as well as in the developing kidney. It further produces a phenotype reminiscent of defective cilia. Moreover, one of the hypertension-associated GRK4 variants appears to be unable to rescue the cilia defects suggesting that at least this variant is not a full gain-of-function in aspects unrelated to dopamine receptors. Therefore we hypothesized that the compromised kidney function in GRK4 SNP carriers may also be attributed to faulty cilia. We will test this hypothesis using a zebrafish loss-of-function model, a heterologous cell system and tissue of mice expressing human GRK4 variants. These mice mirror the hypertensive phenotype seen in patients and are thus a valuable tool to confirm and corroborate data obtained in cells and zebrafish.

Involved staff


Faculty of Medicine
University of Tübingen

Local organizational units

Department of Experimental and Clinical Pharmacology and Pharmacogenomics
Hospitals and clinical institutes, Faculty of Medicine


Bonn, Nordrhein-Westfalen, Germany

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