1. It has been suggested that a dominant mutation in the mouse is a suitable model for the most frequent form of human vitamin D-resistant rickets, X-linked hypophosphataemia. The mutant mice have reduced tubular reabsorption of phosphate, hypophosphataemia, rachitic bone lesions, moderate dwarfism and mild hypocalcaemia.
2. The present work shows that male hypophosphataemic (HYP/Y) mice have a decrease in the tubular capacity to reabsorb calcium as compared with normal littermates (+/Y). This decrease appears to be related to the phosphate status of the animals, since it is much more pronounced when the animals are fed on a low phosphorus diet.
3. The decrement in the tubular reabsorption and plasma concentration of calcium in HYP/Y mice is not accompanied by an augmentation in the absolute urinary excretion of calcium. It is associated with an increase in the urinary excretion of cyclic AMP. Furthermore, removal of the thyroparathyroid glands leads to much larger fall in the plasma concentration of calcium in HYP/Y than in +/Y mice.
4. Thus HYP/Y mice, when compared with normal littermates, have decreased tubular reabsorption of calcium with no apparent increase in the mobilization of calcium from intestinal and body sources as reflected by the absence of an augmentation in the absolute amount of calcium excreted in the urine. These findings could account for a propensity to hypocalcaemia which would be partially compensated by secondary hyperparathyroidism. This could explain the increase in urinary cyclic AMP excretion and the exaggerated hypocalcaemic response to removal of the parathyroid glands observed in murine X-linked hypophosphataemia.