Parabiosis suggests a humoral factor is involved in X ‐linked hypophosphatemia in mice

Reduced renal tubular reabsorption of phosphate of unknown etiology is characteristic of X ‐linked hypophosphatemia in both humans and mice. To test whether a humoral abnormality is involved in the renal effect, parabiosis was performed between Hyp and normal mice at 4 weeks of age. The normal mice joined to Hyp mice showed a progressive diminution of plasma phosphate over the next 3 weeks to approach the level of the Hyp mice. These normal mice had a greater renal phosphate excretion index (urine P/plasma P/urine creatinine) than normal‐normal pairs, thus suggesting a reduced renal tubular reabsorption of phosphate. At the same time the expected rises in plasma calcium and plasma 1,25‐dihydroxyvitamin D did not occur. There was a significant reduction in their femoral mineral content but not in their femoral length or body growth relative to normal‐normal pairs. This change in renal handling of phosphate was specific since the urinary losses of potassium and magnesium were not significantly changed. Separation of normal‐ Hyp pairs 3 or 6 weeks after parabiosis caused the normal mice to achieve normal plasma phosphate levels within 24 h. At 48 h and 7 days after separation these normal mice had plasma phosphate levels higher than normal mice separated from normal‐normal pairs. In summary, the data suggest the presence of a phosphaturic factor in the Hyp mice that can cross a parabiotic union into normal mice and induce many of the symptoms of X ‐linked hypophosphatemia.