Increased plasma 1,25-dihydroxyvitamin D after low calcium challenge in X-linked hypophosphatemic mice

Hyp mice are a model for human X-linked hypophosphatemic (vitamin D-resistant) rickets. We have reported reduced plasma 25-hydroxyvitamin D (25OHD) and normal plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels and (2) failure of low phosphate diets to increase plasma 1,25-(OH)2D in Hyp mice. In this study, we tested the other principal regulatory system of plasma 1,25-(OH)2D by challenging with a low calcium diet. Normal and Hy p mice were fed a control or a low calcium diet for 3 or 7 days. Both normal and Hyp mice showed unchanged plasma phosphate levels and slightly but significantly reduced plasma calcium levels on the low calcium diet. The Hyp mice had significantly elevated plasma parathyroid hormone levels while on the low calcium diet. Plasma 25OHD and 1,25-(OH)2D were measured in the same 4-ml plasma sample by modifications of the Eisman method for 1,25-(OH)2D and the competitive binding assay of Haddad for 25OHD. Each sample was the pooled plasma of 10-14 mice at 13 weeks of age. On the control diet, plasma 1,25-(OH)2D levels were not significantly different in Hyp and normal mice. Plasma 1,25-(OH)2D was elevated in both genotypes on the low calcium diet, but the level in Hyp animals was significantly (P less than 0.05) higher than the level in normal mice. Plasma 25OHD was lower in Hyp than normal and was unaffected by the low calcium diet in either genotype. In summary, whereas Hyp mice do not respond to low phosphate challenge with elevated plasma 1,25-(OH)2D levels, they do respond to low calcium challenge.