Intestinal Depletion of NaPi‐IIb/Slc34a2 in Mice: Renal and Hormonal Adaptation. (7th May 2015)

• Record Type: Journal Article
• Authors: Hernando, Nati; Myakala, Komuraiah; Simona, Fabia; Knöpfel, Thomas; Thomas, Linto; Murer, Heini; Wagner, Carsten A; Biber, Jürg
• Is Part Of: Journal of bone and mineral research. Volume 30:Number 10(2015:Oct.)
• Page Start: 1925
• Page End: 1937
• Publication Date: 2015-05-07
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.2523
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jbmr2523-sec-0001" sec-type="section"> <p>The Na<sup>+</sup>‐dependent phosphate‐cotransporter NaPi‐IIb (SLC34A2) is widely expressed, with intestine, lung, and testis among the organs with highest levels of mRNA abundance. In mice, the intestinal expression of NaPi‐IIb is restricted to the ileum, where the cotransporter localizes specifically at the brush border membrane (BBM) and mediates the active transport of inorganic phosphate (Pi). Constitutive full ablation of NaPi‐IIb is embryonically lethal whereas the global but inducible removal of the transporter in young mice leads to intestinal loss of Pi and lung calcifications. Here we report the generation of a constitutive but intestinal‐specific NaPi‐IIb/<italic>Slc34a2</italic>–deficient mouse model. Constitutive intestinal ablation of NaPi‐IIb results in viable pups with normal growth. Homozygous mice are characterized by fecal wasting of Pi and complete absence of Na/Pi cotransport activity in BBM vesicles (BBMVs) isolated from ileum. In contrast, the urinary excretion of Pi is reduced in these animals. The plasma levels of Pi are similar in wild‐type and NaPi‐IIb–deficient mice. In females, the reduced phosphaturia associates with higher expression of NaPi‐IIa and higher Na/Pi cotransport activity in renal BBMVs, as well as with reduced plasma levels of intact FGF‐23. A similar trend is found in males. Thus, NaPi‐IIb is the only luminal Na<sup>+</sup>‐dependent Pi transporter in the murine ileum and its absence is fully compensated for in adult females by a mechanism involving the bone‐kidney axis. The contribution of this mechanism to the adaptive response is less apparent in adult males. © 2015 American Society for Bone and Mineral Research.</p> </sec> </abstract>