Deletion of claudin-10 rescues claudin-16–deficient mice from hypomagnesemia and hypercalciuria.

Breiderhoff, Tilman, Himmerkus, Nina, Drewell, Hoora, Plain, Allein, Günzel, Dorothee, Mutig, Kerim, Willnow, Thomas E., Müller, Dominik and Bleich, Markus (2017) Deletion of claudin-10 rescues claudin-16–deficient mice from hypomagnesemia and hypercalciuria. Kidney International, 93 . DOI 10.1016/j.kint.2017.08.029.

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Supplementary data:

Abstract

The tight junction proteins claudin-10 and -16 are crucial for the paracellular reabsorption of cations along the thick ascending limb of Henle’s loop in the kidney. In patients, mutations in CLDN16 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis, while mutations in CLDN10 impair kidney function. Mice lacking claudin-16 display magnesium and calcium wasting, whereas absence of claudin-10 results in hypermagnesemia and interstitial nephrocalcinosis. In order to study the functional interdependence of claudin-10 and -16 we generated double-deficient mice. These mice had normal serum magnesium and urinary excretion of magnesium and calcium and showed polyuria and sodium retention at the expense of increased renal potassium excretion, but no nephrocalcinosis. Isolated thick ascending limb tubules of double mutants displayed a complete loss of paracellular cation selectivity and functionality. Mice lacking both claudin-10 and -16 in the thick ascending limb recruited downstream compensatory mechanisms and showed hypertrophic distal convoluted tubules with changes in gene expression and phosphorylation of ion transporters in this segment, presumably triggered by the mild decrease in serum potassium. Thus, severe individual phenotypes in claudin-10 and claudin-16 knockout mice are corrected by the additional deletion of the other claudin.

Document Type: Article
Keywords: calcium claudin magnesium paracellular pathway thick ascending limb tight junction
Research affiliation: Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
Refereed: Yes
Open Access Journal?: No
DOI etc.: 10.1016/j.kint.2017.08.029
ISSN: 0085-2538
Projects: Future Ocean
Date Deposited: 02 Feb 2018 11:27
Last Modified: 23 Apr 2019 12:55
URI: http://oceanrep.geomar.de/id/eprint/41802

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