Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium

Jianghui Hou, Qixian Shan, Tong Wang, Antonio S. Gomes, Qing Shang Yan, David L. Paul, Markus Bleich, Daniel A. Goodenough

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a human disorder caused by mutations in the tight junction protein claudin-16. However, the molecular mechanisms underlining the renal handling of magnesium and its dysfunction causing FHHNC are unknown. Here we show that claudin-16 plays a key role in maintaining the paracellular cation selectivity of the thick ascending limbs of the nephron. Using RNA interference, we have generated claudin-16-deficient mouse models. Claudin-16 knock-down (KD) mice exhibit chronic renal wasting of magnesium and calcium and develop renal nephrocalcinosis. Our data suggest that claudin-16 forms a non-selective paracellular cation channel, rather than a selective Mg2+/Ca 2+ channel as previously proposed. Our study highlights the pivotal importance of the tight junction in renal control of ion homeostasis and provides answer to the pathogenesis of FHHNC. We anticipate our study to be a starting point for more sophisticated in vivo analysis of tight junction proteins in renal functions. Furthermore, tight junction proteins could be major targets of drug development for electrolyte disorders.

Original languageEnglish
Pages (from-to)17114-17122
Number of pages9
JournalJournal of Biological Chemistry
Issue number23
StatePublished - Jun 8 2007


Dive into the research topics of 'Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium'. Together they form a unique fingerprint.

Cite this