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Renal expression of Na+-phosphate cotransporter mRNA and protein: Effect of the Gy mutation and low phosphate diet

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Abstract

The X-linked Gy mutation is closely linked, but not allelic, to Hyp and is characterized by rickets, hypophosphatemia, decreased renal tubular maximum for phosphate (Pi) reabsorption (TmP) and a specific reduction in renal brush-border membrane (BBM) Na+-Pi cotransport. Gy mice, like their normal litter-mates, respond to a low-Pi diet with an increase in BBM Na+-Pi cotransport, but fail to show an adaptive increase in Tmp. Using an antibody raised against the NH2 terminal peptide of the rat renal-specific Na+-Pi cotransporter (NaPi-2) and a NaPi-2 cDNA probe, we examined the effect of the Gy mutation and low-Pi diet (0.03% Pi) on NaPi-2 protein and mRNA abundance. The reduction in BBM Na+-Pi cotransport in Gy mice (51 ± 5% of normal, P < 0.05) was associated with a decrease in NaPi-2 protein (46 ± 12% of normal, P < 0.05) and mRNA abundance (76 ± 5%, P < 0.05). The low-Pi diet elicited a two-to three-fold increase in Na+-Pi cotransport in both normal and Gy mice that was accompanied by a large increase in NaPi-2 protein (10.2-fold in normal and 16.9-fold in Gy mice) and a modest increase in NaPi-2 mRNA (1.3-fold in both mouse strains, P < 0.05). The present data demonstrate that (1) the renal defect in BBM Pi transport in Gy mice can be ascribed to a deficit in NaPi-2 protein and mRNA abundance, (2) both normal and Gy mice respond to low Pi with an adaptive increase in NaPi-2 protein that exceeds the increase in Na+-Pi cotransport activity and NaPi-2 mRNA, (3) the adaptive increase in NaPi-2 protein and mRNA are not sufficient for the overall increase in TmP following Pi restriction.

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Authors and Affiliations

  1. Department of Pediatrics and Human Genetics, McGill University, H3H1P3, Montreal, Canada

    Laurent Beck & Harriet S. Tenenhouse

  2. Department of Orthopaedic Surgery, Carolinas Medical Center, 28232-2861, Charlotte, NC, USA

    Ralph A. Meyer & Martha H. Meyer

  3. Institute of Physiology, University of Zürich, CH-8057, Zürich, Switzerland

    Jürg Biber & Heini Murer

Authors
  1. Laurent Beck
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  2. Ralph A. Meyer
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  3. Martha H. Meyer
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  4. Jürg Biber
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  5. Heini Murer
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  6. Harriet S. Tenenhouse
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Additional information

A portion of these data has been presented in abstract form: Beck L, Meyer RA Jr, Meyer MH, Biber J, Murer H, Tenenhouse HS (1995) Effect of the X-linked Gy mutation and low phosphate diet on the renal brush-border membrane Na+-phosphate cotransport protein. J Am Soc Nephrol 6:943

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Beck, L., Meyer, R.A., Meyer, M.H. et al. Renal expression of Na+-phosphate cotransporter mRNA and protein: Effect of the Gy mutation and low phosphate diet. Pflügers Arch. 431, 936–941 (1996). https://doi.org/10.1007/s004240050088

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  • DOI: https://doi.org/10.1007/s004240050088

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