PARATHYROID-HORMONE GENE-EXPRESSION IN HYP MICE FED A LOW-PHOSPHATE DIET

Background, The murine analogue of X-linked hypophosphataemia is the H yp mouse; it has chronic phosphate depletion from an inherited defect of renal tubular reabsorption. Phosphate directly regulates the parath yroid (PT) in normal rats and it is of interest whether this regulatio n is intact in Hyp mice. Methods. Hyp mice were fed either a low-phosp hate diet or control diet and PTH mRNA levels were measured. In additi on changes in NMR-visible kidney and muscle intracellular phosphate po tentials in normal and Hyp mice were determined. Mice were maintained on a low-phosphate (0.02%) or normal-phosphate (0.6%) diet for 24 and 72 h. Results. On the normal diet, Hyp mice had hypophosphataemia, nor mocalcaemia, and normal PTH mRNA levels. Phosphate deprivation for 72 h led to a profound fall in plasma phosphate, a slight but significant rise in plasma calcium, and a dramatic decrease in PTH mRNA, similar to that of normal mice fed this diet. Changes in kidney and muscle int racellular phosphate measured by NMR spectroscopy were not affected by diet or genotype. Conclusion. Dietary phosphate deprivation decreased Hyp mice PTH mRNA levels and caused no change in intracellular phosph ate potentials. Therefore Hyp mice parathyroids' adapt appropriately t o phosphate deprivation albeit at a lower threshold compared to normal mice.