Specific disruption of calcineurin-signaling in the distal convoluted tubule impacts the transcriptome and proteome, and causes hypomagnesemia and metabolic acidosis

Adverse effects of calcineurin inhibitors (CNI), such as hypertension, hyperkalemia, acidosis, hypomagnesemia and hypercalciuria, have been linked to dysfunction of the distal convoluted tubule (DCT). To test this, we generated a mouse model with an inducible DCT-specific deletion of the calcineurin regulatory subunit B alpha (CnB1-KO). Three weeks after CnB1 deletion, these mice exhibited hypomagnesemia and acidosis, but no hypertension, hyperkalemia or hypercalciuria. Consistent with the hypomagnesemia, CnB1-KO mice showed a downregulation of proteins implicated in DCT magnesium transport, including TRPM6, CNNM2, SLC41A3 and parvalbumin but expression of calcium channel TRPV5 in the kidney was unchanged.

Source: Kidney International - July 9, 2021 Category: Urology & Nephrology Authors: Eszter Banki, Viktoria Fisi, Sandra Moser, Agnieszka Wengi, Monique Carrel, Dominique Loffing-Cueni, David Penton, Denise V. Kratschmar, Ludovica Rizzo, Soeren Lienkamp, Alex Odermatt, Markus M. Rinschen, Johannes Loffing Tags: basic research Source Type: research