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Hypertension is a major health problem throughout the world because of its high prevalence and its association with increased risk of cardiovascular disease. Two independent studies discovered a locus conferring susceptibility to essential hypertension on chromosome 2, in the 2p25 region, but the causative gene remains unknown. Grainyhead-like 1 (GRHL1) is one of the genes located in this region. Our experiments determined that the Grhl1 -null mice, when fed standard diet, have the same blood pressure as their wild type littermate controls. However, we discovered that blood pressure of these mice increases following high sodium diet and decreases when they are fed low sodium diet, and similar effects were not observed in the control wild type littermates. This suggests that the Grhl1 -null mice are sensitive to the development of salt-sensitive hypertension. Thus it is possible that the GRHL1 gene is involved in the regulation of blood pressure, and it may be the causative gene for the locus of susceptibility to essential hypertension in the 2p25 region.

Effects of High and Low Sodium Diet on Blood Pressure and Heart Rate in Mice Lacking the Functional Grainyhead-Like 1 Gene