Endocrinology, Vol 131, 51-56, Copyright © 1992 by Endocrine Society

ARTICLES

Renal phosphate transport and vitamin D metabolism in X-linked hypophosphatemic Gy mice: responses to phosphate deprivation

HS Tenenhouse, RA Meyer Jr, S Mandla, MH Meyer and RW Gray
Department of Pediatrics, McGill University, Montreal, Quebec, Canada.

Two closely linked, nonallelic genes, Gy and Hyp, result in X-linked hypophosphatemia in mice. The present studies in Gy mice were undertaken to determine whether renal brush-border membrane Na(+)- phosphate cotransport kinetics and adaptive responses of renal phosphate transport and vitamin D metabolism to phosphate deprivation are comparable in the two mutant strains. Transport studies in purified brush-border membrane vesicles over a phosphate concentration range of 10-500 microM demonstrated that the apparent maximum velocity of the high affinity transport system is significantly decreased in Gy mice (420 +/- 110 vs. 710 +/- 100 pmol/mg protein.6 sec, Gy vs. normal; mean +/- SE; P less than 0.05), whereas the affinity of the cotransporter for phosphate is unchanged (apparent Km, 25 +/- 3 vs. 27 +/- 2 microM; NS). Feeding a low phosphate diet results in a significant fall in plasma phosphate and an increase in brush-border membrane Na(+)- phosphate cotransport in both normal (568 +/- 40 to 1416 +/- 139 pmol/mg protein.6 sec; P less than 0.01) and Gy mice (407 +/- 27 to 1236 +/- 132 pmol/mg protein.6 sec; P less than 0.01). While the low phosphate diet elicited a rise in plasma 1,25-dihydroxyvitamin D in normal mice (51 +/- 12 to 158 +/- 12 pM; P less than 0.01), a fall in plasma hormone levels was evident in phosphate-deprived Gy mice (90 +/- 22 to 23 +/- 11 pM; P less than 0.01). Phosphate deprivation decreased 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase), the first enzyme in the renal vitamin D catabolic pathway, in normal mice (117 +/- 21 to 69 +/- 8 fmol/mg protein.min), but increased enzyme activity in Gy mice (172 +/- 14 to 240 +/- 18 fmol/mg protein.min; P less than 0.05). Moreover, under both dietary conditions, 24-hydroxylase activity was significantly elevated in Gy mice. The present results demonstrate that hypophosphatemia in Gy mice can be attributed to a decrease in the maximum velocity of the high affinity Na(+)-phosphate cotransport process in renal brush-border membranes. Our results also show that while renal brush-border membrane phosphate transport is appropriately modulated by phosphate in Gy mice, phosphate regulation of vitamin D metabolism is apparently impaired in the mutant strain. The present findings provide evidence for phenotypic similarities between murine Gy and Hyp mutations.

This article has been cited by other articles:

				M. H. Meyer, E. Dulde, and R. A. Meyer Jr. The genomic response of the mouse kidney to low-phosphate diet is altered in X-linked hypophosphatemia Physiol Genomics, June 17, 2004; 18(1): 4 - 11. [Abstract] [Full Text] [PDF]

				H. S. Tenenhouse, J. Martel, C. Gauthier, M. Y. H. Zhang, and A. A. Portale Renal Expression of the Sodium/Phosphate Cotransporter Gene, Npt2, Is Not Required for Regulation of Renal 1{{alpha}}-Hydroxylase by Phosphate Endocrinology, March 1, 2001; 142(3): 1124 - 1129. [Abstract] [Full Text] [PDF]

				M. J. Econs and F. Francis Positional cloning of the PEX gene: new insights into the pathophysiology of X-linked hypophosphatemic rickets Am J Physiol Renal Physiol, October 1, 1997; 273(4): F489 - F498. [Abstract] [Full Text] [PDF]