title: Abnormal regulation of renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the X-linked hypophosphatemic mouse.
abstract: Abnormal vitamin D metabolism has been suspected in patients with X-linked hypophosphatemic rickets (XLH) and X-linked hypophosphatemic mice (Hyp-mice), the murine homologue of the human disease. We compared 25(OH)D-1 alpha-hydroxylase activity in the Hyp-mouse kidney to that in normal and phosphate-depleted mouse kidney. Weanling normal and Hyp-mice were fed a 0.6% phosphorus diet; phosphate-depleted mice received a 0.02% phosphorus diet. At 8-10 wk of age the serum phosphorus values in Hyp (3.35 +/- 0.12 mg/dl) and phosphate-depleted mice (3.83 +/- 0.56) were not significantly different. Despite the similar magnitude of phosphate depletion, however, the maximum levels of 25(OH)D-1 alpha-hydroxylase activity were disparate: phosphate-depleted mouse kidney had profoundly increased activity compared to normal (17.04 +/- .104 vs. 4.96 +/- 0.23 fmol 1,25(OH)2D3 produced/mg kidney per min) while Hyp-mouse kidney had a fourfold lesser increment (8.18 +/- 0.62). These data indicate that phosphate depletion is a potent stimulus of 25(OH)D-1 alpha-hydroxylase activity in the (C57BL6J) mouse. Moreover, the results show that abnormal regulation of 25(OH)D-1 alpha-hydroxylase activity is manifest in the Hyp-mouse.
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000818:Animals; D005260:Female; D007015:Hypophosphatemia, Familial / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010758:Phosphorus / Q000172:deficiency; D012729:Sex Chromosome Aberrations / Q000201:enzymology*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013997:Time Factors; D014960:X Chromosome
chemical_list: D010758:Phosphorus; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase