Magdalena Pawlak1, Agnieszka Walkowska2, Michał Mlącki1, Jelena Pistolic3, Tomasz Wrzesiński4, Vladimir Benes3, Stephen M Jane5, Joanna Wesoły4, Elżbieta Kompanowska-Jezierska2, Tomasz Wilanowski1. 1. Laboratory of Signal Transduction, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland. 2. Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. 3. Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany. 4. Laboratory of High Throughput Technologies, Institute of Biotechnology and Molecular Biology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland. 5. Department of Medicine, Monash University Central Clinical School, Prahran VIC, Australia; and Alfred Hospital, Prahran VIC, Australia.
Abstract
AIM: 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. EXPERIMENTAL APPROACH: 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. CONCLUSIONS: 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.
AIM: 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. EXPERIMENTAL APPROACH: 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. CONCLUSIONS: 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.
Authors: Jemma G Gasperoni; Jarrad N Fuller; Charbel Darido; Tomasz Wilanowski; Sebastian Dworkin Journal: Int J Mol Sci Date: 2022-03-01 Impact factor: 6.208