EFFECTS OF ALTERED DIET ON SERUM LEVELS OF 1,25-DIHYDROXYVITAMIN-D AND PARATHYROID-HORMONE IN X-LINKED HYPOPHOSPHATEMIC (HYP AND GY) MICE

X-linked hypophosphatemia is a metabolic bone disease occurring in bot h humans and mice. In mice, two different mutations (Hyp and Gy), occu rring at separate but closely linked loci, have been proposed as model s for this disease, Varying reports of the Vitamin D status of these t wo mutants has led us to reexamine the influence of diet on circulatin g calcitrophic hormones and mineral metabolism in both mutants. Hyp an d Gy mice were raised on the B6C3H background, and both normal females and heterozygous mutant females were studied at 10 weeks of age. Anim als were fed one of three diets at random: high (1.5% Ca and 1.0% P); medium (0.6% Ca and 0.6% P); or low (0.0% Ca and 0.6% P). After 3 days , serum and urine samples were collected. In comparison to mutant mice fed the high diet, both Hyp and Gy mice fed the low diet had decrease d serum calcium levels, and further elevations in both serum alkaline phosphatase and serum parathyroid hormone (PTH), Serum 1,25-dihydroxyv itamin D levels were elevated by both the medium and low diets in all groups of mice over values obtained with the high diet. Mutant mice we re significantly higher in serum PTH on all diets compared to normal m ice fed the same diet. Mutant mice were not elevated in serum 1,25-dih ydroxyvitamin D over normal mice when fed the high diet. However, both Hyp and Gy mice fed the medium and low diets were elevated in serum 1 ,25-dihydroxyvitamin D over normal mice. Serum PTH levels were correla ted to serum 1,25-dihydroxyvitamin D levels with Hyp and Gy mice lying on the same line (r = 0.86; p < 0.0001). In summary, when Hyp and Gy mice are studied on the same genetic background and fed the same diet, similar responses are seen in PTH levels and 1,25-dihydroxyvitamin D levels. Both mutants should be useful in elucidating the pathophysiolo gy of this poorly understood human disease.