Journal Article

<i>Dkk3</i> is a component of the genetic circuitry regulating aldosterone biosynthesis in the adrenal cortex

Abeer El Wakil, Sascha Bandulik, Nicolas Guy, Saïd Bendahhou, Maria-Christina Zennaro, Christof Niehrs, Bernard Mari, Richard Warth, Jacques Barhanin and Enzo Lalli

in Human Molecular Genetics

Volume 21, issue 22, pages 4922-4929
Published in print November 2012 | ISSN: 0964-6906
Published online August 2012 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/dds333
Dkk3 is a component of the genetic circuitry regulating aldosterone biosynthesis in the adrenal cortex

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Primary aldosteronism (PA, autonomous aldosterone production from the adrenal cortex) causes the most common form of secondary arterial hypertension (HT), which is also the most common curable form of HT. Recent studies have highlighted an important role of mutations in genes encoding potassium channels in the pathogenesis of PA, both in human disease and in animal models. Here, we have exploited the unique features of the hyperaldosteronemic phenotype of Kcnk3 null mice, which is dependent on sexual hormones, to identify genes whose expression is modulated in the adrenal gland according to the dynamic hyperaldosteronemic phenotype of those animals. Genetic inactivation of one of the genes identified by our strategy, dickkopf-3 (Dkk3), whose expression is increased by calcium influx into adrenocortical cells, in the Kcnk3 null background results in the extension of the low-renin, potassium-rich diet insensitive hyperaldosteronemic phenotype to the male sex. Compound Kcnk3/Dkk3 animals display an increased expression of Cyp11b2, the rate-limiting enzyme for aldosterone biosyntheis in the adrenal zona glomerulosa (ZG). Our data show that Dkk3 can act as a modifier gene in a mouse model for altered potassium channel function and suggest its potential involvement in human PA syndromes.

Journal Article.  4293 words.  Illustrated.

Subjects: Genetics and Genomics

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