Key result
ERRgamma knockout kills mice within 72 hours, driven by elevated potassium and prolonged QT arrhythmias.
Why the study?
The orphan nuclear receptor ERRgamma coordinates expression of genes central to ion homeostasis in oxidative tissues, but its role in cardiac, gastric, and renal potassium homeostasis was unclear.
ERRgamma plays a critical role in regulating genes central to ion homeostasis, and its absence leads to fatal hyperkalemia and cardiac arrhythmias with prolonged QT intervals in perinatal mice.
ESRRG variants were associated with blood pressure; leaves open whether ERRγ modulation influences arrhythmia or electrolyte disorders in patients.
Energy production by oxidative metabolism in kidney, stomach, and heart, is primarily expended in establishing ion gradients to drive renal electrolyte homeostasis, gastric acid secretion, and cardiac muscle contraction, respectively. In addition to orchestrating transcriptional control of oxidative metabolism, the orphan nuclear receptor, estrogen-related receptor gamma (ERRgamma), coordinates expression of genes central to ion homeostasis in oxidative tissues. Renal, gastric, and cardiac tissues subjected to genomic analysis of expression in perinatal ERRgamma null mice revealed a characteristic dysregulation of genes involved in transport processes, exemplified by the voltage-gated potassium channel, Kcne2. Consistently, ERRgamma null animals die during the first 72 h of life with elevated serum potassium, reductions in key gastric acid production markers, and cardiac arrhythmia with prolonged QT intervals. In addition, we find altered expression of several genes associated with hypertension in ERRgamma null mice. These findings suggest a potential role for genetic polymorphisms at the ERRgamma locus and ERRgamma modulators in the etiology and treatment of renal, gastric, and cardiac dysfunction.
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Alaynick et al. (2009) studied ERRgamma null mutation. ERRgamma null mutation was evaluated on Survival, serum potassium, gastric acid production markers, and cardiac arrhythmia. ERRgamma null mice die within the first 72 hours of life, exhibiting elevated serum potassium, reduced gastric acid production markers, and cardiac arrhythmia with prolonged QT intervals.
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