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Hypophosphatemia in vitamin D receptor null mice: effect of rescue diet on the developmental changes in renal Na+-dependent phosphate cotransporters

Pflügers Archiv - European Journal of Physiology volume 461, pages 77–90 (2011)Cite this article

Abstract

We analyzed vitamin D receptor (VDR) (−/−) mice fed either a normal diet or a rescue diet. Weanling VDR (−/−) mice had hypophosphatemia and hyperphosphaturia. Renal Na+-dependent inorganic phosphate (Pi) cotransport activity was significantly decreased in weanling VDR (−/−) mice. In VDR (+/+) mice, renal Npt2a/Npt2c/PiT-2 protein levels were significantly increased at 21 and 28 days of age compared with that at 1 day of age. Npt2c and PiT-2 protein levels were maximally expressed at 28 days of age. Npt2a protein levels were significantly decreased in mice at 28 days of age compared with 21 and 60 days of age. In VDR (−/−) mice, Npt2a/Npt2c/PiT-2 protein levels were considerably lower than those in age-matched VDR (+/+) mice at 21 and 28 days of age. The reduced Npt2a/Npt2c/PiT-2 protein recovered completely in VDR-null mice fed the rescue diet. Although Pi transport activity and Npt2b were reduced in the proximal intestine in VDR (−/−) mice, Npt2b protein levels were not reduced in the distal intestine in VDR (−/−) mice. The rescue diet did not affect intestinal Npt2b protein levels in VDR (−/−) mice. Thus, reduced intestinal Pi absorption in VDR (−/−) mice does not seem to be the only factor that causes hypophosphatemia; reduced Npt2a, Npt2c, or PiT-2 protein levels during development might also cause hypophosphatemia and rickets in VDR (−/−) mice. Furthermore, dietary intervention completely normalized the expression of the renal phosphate transporters (Npt2a/Npt2c/PiT-2) in VDR (−/−) mice, suggesting that the lack of VDR activity is not the cause of impaired renal phosphate reabsorption.

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Acknowledgment

This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (no. 19790585 to H. Segawa and no. 20390236 to K. Miyamoto).

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Affiliations

  1. Department of Molecular Nutrition, Institution of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-Cho 3, Tokushima, 770-8503, Japan

    Ichiro Kaneko, Hiroko Segawa, Junya Furutani, Shoji Kuwahara, Fumito Aranami, Etsuyo Hanabusa, Rieko Tominaga & Ken-ichi Miyamoto

  2. Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, Denver, CO, USA

    Hector Giral, Yupanqui Caldas & Moshe Levi

  3. Division of Renal Diseases and Hypertension, Department of Medicine, Veterans Affairs Medical Center, Aurora, CO, USA

    Hector Giral, Yupanqui Caldas & Moshe Levi

  4. Laboratory of Nuclear Signaling, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan

    Shigeaki Kato

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  1. Ichiro Kaneko
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  2. Hiroko Segawa
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  3. Junya Furutani
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  4. Shoji Kuwahara
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  12. Ken-ichi Miyamoto
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Correspondence to Hiroko Segawa or Ken-ichi Miyamoto.

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Kaneko, I., Segawa, H., Furutani, J. et al. Hypophosphatemia in vitamin D receptor null mice: effect of rescue diet on the developmental changes in renal Na+-dependent phosphate cotransporters. Pflugers Arch - Eur J Physiol 461, 77–90 (2011). https://doi.org/10.1007/s00424-010-0888-z

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  • DOI: https://doi.org/10.1007/s00424-010-0888-z

Keywords

  • Phosphate
  • Transporter
  • Kidney
  • Bone
  • Brush-border membrane