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

Teresa Nesbitt, Michael J. Econs, Jong K. Byun, Josée Martel, Harriet S. Tenenhouse, Marc K. Drezner

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Whether renal phosphate wasting in X‐linked hypophosphatemia (XLH) results from an intrinsic renal or humoral defect remains controversial. In studies of the murine homolog of XLH, harboring the Simian Virus 40 (SV40) large T antigen, we obviated the influence of renal cell heterogeneity and impressed memory by comparing Na+‐phosphate cotransport in immortalized cells from the S1 segment of the proximal tubule. Cells from SV40 transgenic normal and Hyp mice exhibit characteristics of differentiated proximal tubule cells including gluconeogenesis and alkaline phosphatase activity. Surprisingly, however, we found two distinct populations of cells from the S1 proximal tubule of both normal and Hyp mice. In one, PTH treatment increases cAMP accumulation, while in the other both PTH and thyrocalcitonin enhance cAMP production. Kinetic parameters for Na+‐phosphate cotransport were similar in both subpopulations of cells from normal (Km, 0.29 ± 0.03 vs. 0.39 ± 0.04 mM; Vmax, 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 importantly, phosphate transport in S1 cells of either subpopulation from Hyp mice is no different than that of normals. These data indicate that renal proximal tubule cells from Hyp mice have intrinsically normal phosphate transport and support the hypothesis that a humoral abnormality underlies renal phosphate wasting in XLH.

Original languageEnglish (US)
Pages (from-to)1327-1333
Number of pages7
JournalJournal of Bone and Mineral Research
Volume10
Issue number9
DOIs
StatePublished - Sep 1995
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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