Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg^sup 2+^ handling

• Published in: American journal of physiology. Renal physiology Vol. 305; no. 11; p. F1563
• Main Authors: de Baaij, Jeroen HF, Koerkamp, Marian J Groot, Lavrijsen, Marla, van Zeeland, Femke, Meijer, Hans, Holstege, Frank CP, Bindels, René JM, Hoenderop, Joost GJ
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.12.2013
• Subjects: Gene expression; Homeostasis; Kidney diseases; Kidneys; Magnesium; Proteins
• ISSN: 1931-857X; 1522-1466

The kidney plays a key role in the maintenance of ... homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal ... handling. In recent years, hereditary ... transport disorders have helped to identify important players in DCT ... homeostasis. Nevertheless, several proteins involved in DCT-mediated ... reabsorption remain to be discovered, and a full expression profile of this complex nephron segment may facilitate the discovery of new ...-related genes. Here, we report ...-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 ...-deficient or ...-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 ... to identify ... 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 ... Moreover, new genes were identified that are potentially involved in renal ... handling. To confirm that the selected candidate genes were regulated by dietary ... availability, the expression levels of solute carrier family 41, member 3 (Slc41a3), pterin-4 a-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1a (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 ...-deficient diet. By elucidating the ...-sensitive DCT transcriptome, new candidate genes in renal ... handling have been identified. (ProQuest: ... denotes formulae/symbols omitted.)