Consequences of the loss of the Grainyhead-like 1 gene for renal gene expression, regulation of blood pressure and heart rate in a mouse model.

Magdalena Pawlak; Agnieszka Walkowska; Michał Mlącki; Jelena Pistolic; Tomasz Wrzesiński; Vladimir Benes; Stephen M Jane; Joanna Wesoły; Elżbieta Kompanowska-Jezierska; Tomasz Wilanowski

Magdalena Pawlak Laboratory of Signal Transduction, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.;
Agnieszka Walkowska Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.;
Michał Mlącki Laboratory of Signal Transduction, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.;
Jelena Pistolic Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany.;
Tomasz Wrzesiński Laboratory of High Throughput Technologies, Institute of Biotechnology and Molecular Biology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland.;
Vladimir Benes Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany.;
Stephen M Jane Department of Medicine, Monash University Central Clinical School, Prahran VIC, Australia; and Alfred Hospital, Prahran VIC, Australia.;
Joanna Wesoły Laboratory of High Throughput Technologies, Institute of Biotechnology and Molecular Biology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland.;
Elżbieta Kompanowska-Jezierska Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.;
Tomasz Wilanowski Laboratory of Signal Transduction, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.;

Abstract

The Grainyhead-like 1 (GRHL1) transcription factor is tissue-specific and is very highly expressed in the kidney. In humans the GRHL1 gene is located at the chromosomal position 2p25. A locus conferring increased susceptibility to essential hypertension has been mapped to 2p25 in two independent studies, but the causative gene has never been identified. Furthermore, a statistically significant association has been found between a polymorphism in the GRHL1 gene and heart rate regulation. The aim of our study was to investigate the physiological consequences of Grhl1 loss in a mouse model and ascertain whether Grhl1 may be involved in the regulation of blood pressure and heart rate. In our research we employed the Grhl1 "knock-out" mouse strain. We analyzed renal gene expression, blood pressure and heart rate in the Grhl1-null mice in comparison with their "wild-type" littermate controls. Most important results: The expression of many genes is altered in the Grhl1(-/-) kidneys. Some of these genes have previously been linked to blood pressure regulation. Despite this, the Grhl1-null mice have normal blood pressure and interestingly, increased heart rate. Our work did not discover any new evidence to suggest any involvement of Grhl1 in blood pressure regulation. However, we determined that the loss of Grhl1 influences the regulation of heart rate in a mouse model.