Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg2+ handling

Jeroen H.F. de Baaij, Marian J. Groot Koerkamp, Marla Lavrijsen, Femke van Zeeland, Hans Meijer, Frank C.P. Holstege, René J.M. Bindels, Joost G.J. Hoenderop

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

42 Citaten (Scopus)


The kidney plays a key role in the maintenance of Mg2+ homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg2+ handling. In recent years, hereditary Mg2+ transport disorders have helped to identify important players in DCT Mg2+ homeostasis. Nevertheless, several proteins involved in DCT-mediated Mg2+ reabsorption remain to be discovered, and a full expression profile of this complex nephron segment may facilitate the discovery of new Mg2+-related genes. Here, we report Mg2+-sensitive expression of the DCT transcriptome. To this end, transgenic mice expressing enhanced green fluorescent protein under a DCT-specific parvalbumin promoter were subjected to Mg2+-deficient or Mg2+-enriched diets. Subsequently, the Complex Object Parametric Analyzer and Sorter allowed, for the first time, isolation of enhanced green fluorescent protein-positive DCT cells. RNA extracts thereof were analyzed by DNA microarrays comparing high versus low Mg2+ to identify Mg2+ regulatory genes. Based on statistical significance and a fold change of at least 2, 46 genes showed differential expression. Several known magnesiotropic genes, such as transient receptor potential cation channel, subfamily M, member 6 (Trpm6), and Parvalbumin, were upregulated under low dietary Mg2+. Moreover, new genes were identified that are potentially involved in renal Mg2+ handling. To confirm that the selected candidate genes were regulated by dietary Mg2+ availability, the expression levels of solute carrier family 41, member 3 (Slc41a3), pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α (Pcbd1), TBC1 domain family, member 4 (Tbc1d4), and uromodulin (Umod) were determined by RT-PCR analysis. Indeed, all four genes show significant upregulation in the DCT of mice fed a Mg2+-deficient diet. By elucidating the Mg2+-sensitive DCT transcriptome, new candidate genes in renal Mg2+ handling have been identified.

Originele taal-2Engels
Pagina's (van-tot)F1563-F1573
TijdschriftAmerican Journal of Physiology - Renal Physiology
Nummer van het tijdschrift11
StatusGepubliceerd - 1 dec. 2013
Extern gepubliceerdJa


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