Abnormal vitamin D metabolism in the X-linked hypophosphatemic mouse.
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.
D000818:Animals; D002112:Calcifediol; D002117:Calcitriol; D002118:Calcium / Q000097:blood; D004032:Diet; D004100:Dihydroxycholecalciferols / Q000097:blood*; D005260:Female; D006887:Hydroxycholecalciferols / Q000097:blood*; D007015:Hypophosphatemia, Familial / Q000097:blood*; D008274:Magnesium / Q000652:urine; D008297:Male; D051379:Mice; D010758:Phosphorus / Q000008:administration & dosage* / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010758:Phosphorus; D002117:Calcitriol; D008274:Magnesium; D002112:Calcifediol; D002118:Calcium