PHOSPHATE-TRANSPORT IN IMMORTALIZED CELL-CULTURES FROM THE RENAL PROXIMAL TUBULE OF NORMAL AND HYP MICE - EVIDENCE THAT THE HYP GENE LOCUS PRODUCT IS AN EXTRARENAL FACTOR

Whether renal phosphate, wasting in X-linked hypophosphatemia (XLH) re sults from an intrinsic renal or humoral defect remains controversial, In studies of the murine homolog of XLH, harboring the Simian Virus 4 0 (SV40) large T antigen, we obviated the influence of renal cell hete rogeneity and impressed memory by comparing Na+-phosphate cotransport in immortalized cells from the S-1 segment of the proximal tubule, Cel ls from SV40 transgenic normal and Hyp mice exhibit characteristics of differentiated proximal tubule cells including gluconeogenesis and al kaline phosphatase activity, Surprisingly, however, we found two disti nct populations of cells from the S-1 proximal tubule of both normal a nd Hyp mice. In one, PTH treatment increases cAMP accumulation, while in the other both PTH and thyrocalcitonin enhance cAMP production, Kin etic parameters for Na+-phosphate cotransport were similar in both sub populations of cells from normal (K-m, 0.29 +/- 0.03 vs, 0.39 a 0.04 m M; V-max, 4.6 +/- 0.6 vs, 5.2 +/- 0.4 nmol/mg/5 minutes) and Hyp mice (0.33 +/- 0.02 vs, 0.26 +/- 0.04; 6.0 +/- 0.7, 4.8 +/- 0.6). More impo rtantly, phosphate transport in S-1 cells of either subpopulation from Hyp mice is no different than that of normals. These data indicate th at renal proximal tubule cells from Hyp mice have intrinsically normal phosphate transport and support the hypothesis that a humoral abnorma lity underlies renal phosphate wasting in XLH.