Endocrinology, Vol 107, 1577-1581, Copyright © 1980 by Endocrine Society

ARTICLES

Abnormal vitamin D metabolism in the X-linked hypophosphatemic mouse

RA Meyer Jr, RW Gray and MH Meyer

The vitamin D metabolites, 25-hydroxyvitamin D (250HD) and 1,25- dihydroxyvitamin D [1,25-(OH)2D], were measured in samples of plasma from normal and X-linked hypophosphatemic (Hyp) mice, which are a model for this common form a human vitamin D-resistant rickets. Each sample was the pooled plasma from the exsanguination of 10-15 mice. On stock diets plasma 1,25-(OH)2D was the same in Hyp mice as in normal mice [normal vs. Hyp, 70 +/- 4 vs. 66 +/- 4 pM; (mean +/- SE) n = 8; P = NS]. However, plasma 25OHD was lower in Hyp mice (59 +/- 4 vs. 37 +/- 4 nM; n = 6; P < 0.01). Since hypophosphatemia usually elevates plasms 1,25-(OH)2D in rats, we suspected that Hyp mice were unresponsive to hypophosphatemia. To test this, mice were challenged with a low phosphorus (P) diet for 6 days . A low P diet lowered plasma P and raised plasma calcium levels in both normal and Hyp mice. In both genotypes, the low P diet also increased magnesium levels in urine and transiently in plasma. The low P diet raised plasma 1,25-(OH)2D in normal mice, but lowered it in Hyp mice to nondetectable levels. There was no significant effect of the low P diet on plasma levels of 25OHD. We conclude that Hyp mice have a defective control system for plasma levels of 1,25-(OH)2D that does not respond to a low P stimulus with elevated plasma levels of the hormone.

This article has been cited by other articles:

				B. Yuan, Y. Xing, R. L. Horst, and M. K. Drezner Evidence for Abnormal Translational Regulation of Renal 25-Hydroxyvitamin D-1{alpha}-Hydroxylase Activity in the Hyp-Mouse Endocrinology, August 1, 2004; 145(8): 3804 - 3812. [Abstract] [Full Text] [PDF]

				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]

				N. Azam, M. Y. H. Zhang, X. Wang, H. S. Tenenhouse, and A. A. Portale Disordered Regulation of Renal 25-Hydroxyvitamin D-1{alpha}-Hydroxylase Gene Expression by Phosphorus in X-Linked Hypophosphatemic (Hyp) Mice Endocrinology, August 1, 2003; 144(8): 3463 - 3468. [Abstract] [Full Text] [PDF]

				X. Bai, D. Miao, D. Panda, S. Grady, M. D. McKee, D. Goltzman, and A. C. Karaplis Partial Rescue of the Hyp Phenotype by Osteoblast-Targeted PHEX (Phosphate-Regulating Gene with Homologies to Endopeptidases on the X Chromosome) Expression Mol. Endocrinol., December 1, 2002; 16(12): 2913 - 2925. [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]