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Pflügers Archiv

, Volume 444, Issue 5, pp 670–676 | Cite as

Na/Pi cotransporter (Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2

  • Harriet S. Tenenhouse
  • Claude Gauthier
  • Josée Martel
  • Joost G. Hoenderop
  • Anita Hartog
  • Martha H. Meyer
  • Ralph A. Meyer
  • René J. Bindels
Original Article

Abstract.

Mice homozygous for the disrupted type-II Na/Pi cotransporter gene (Npt2 –/–) exhibit hypophosphataemia, increased serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)2D) and calcium (Ca) and elevated urinary Ca excretion. To determine whether the hypercalcaemia and hypercalciuria are secondary to 1,25-(OH)2D-stimulated intestinal Ca absorption, we examined the effect of Npt2 gene disruption on serum Ca and urinary Ca excretion after an overnight fast, and on duodenal Ca absorption. We also compared the duodenal expression of the epithelial Ca channels, ECaC1 and ECaC2, and calbindinD9K mRNAs, relative to that of β-actin mRNA, in Npt2 +/+ and Npt2 –/– mice. Both serum Ca and urine Ca/creatinine were significantly decreased in Npt2 –/– mice after an overnight fast and were no longer different from that in wild-type mice. Absorption of 45Ca from isolated duodenal segments in vivo and 45Ca appearing in the plasma were significantly increased in Npt2 –/– compared with Npt2 +/+ mice. In addition, the duodenal abundance of ECaC1, ECaC2 and calbindinD9K mRNAs was significantly elevated in mutant mice relative to that in wild-type mice. In contrast, both duodenal Ca absorption and ECaC1 and ECaC2 mRNA abundance were lower in mice with X-linked hypophosphataemia (Hyp) than in normal littermates. In summary, we provide evidence for increased duodenal Ca absorption in Npt2 –/– mice and suggest a role for ECaC1, ECaC2 and calbindinD9K in mediating this response.

ECaC CaT1 Hypophosphataemia Hypercalciuria Vitamin D 

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Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Harriet S. Tenenhouse
    • 1
  • Claude Gauthier
    • 1
  • Josée Martel
    • 1
  • Joost G. Hoenderop
    • 2
  • Anita Hartog
    • 2
  • Martha H. Meyer
    • 3
  • Ralph A. Meyer
    • 3
  • René J. Bindels
    • 2
  1. 1.Departments of Pediatrics and Human Genetics, McGill University-Montreal Children's Hospital Research Institute, 2300 Tupper Street, Montreal, Quebec H3H 1P3, Canada
  2. 2.Department of Cell Physiology, Nijmegen Centre for Molecular Life Sciences, University Medical Centre Nijmegen, the Netherlands
  3. 3.Orthopaedic Research Laboratory, Carolinas Medical Center, Charlotte, N.C., USA

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