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.
Meyer
R A
RA
Department of Basic Sciences, Marquette University School of Dentistry, Milwaukee, WI 53233.
Meyer
M H
MH
Gray
R W
RW
D000818:Animals; D001835:Body Weight; D001846:Bone Development; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000652:urine; D005260:Female; D008040:Genetic Linkage; D007015:Hypophosphatemia, Familial / Q000235:genetics* / Q000378:metabolism; D008274:Magnesium / Q000652:urine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010227:Parabiosis; D010710:Phosphates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011188:Potassium / Q000652:urine; D016038:Skin Transplantation; D014960:X Chromosome
D010710:Phosphates; D003404:Creatinine; D008274:Magnesium; D011188:Potassium; D002118:Calcium