Nesbitt T, Byun JK, Drezner MK

Normal phosphate transport in cells from the S2 and S3 segments of Hyp-mouse proximal renal tubules. Endocrinology 1996 Mar;137(3):943-8

An intrinsic phosphate (Pi) transport defect in the proximal tubule(PT) presumably underlies X-linked hypophosphatemic rickets. Werecently reported normal Pi tranor S3 segment remains unknown. Thus, we compared Pi transport in S2and S3 immortalized cells from transgenic (simian virus 40) normaland Hyp mice. These cells display biochemical features of PT cells, including alkaline phosphatase- and hormone- stimulated cAMPactivity as well as gluconeogenesis. Moreover, kinetic studies in S2cells reveal a similar Km[0.26 +/- 0.03 (+/-SEM) vs. 0.22 +/- 0.03 mM] and maximum velocity (Vmax; 5.5 +/- 0.66 vs. 5.9 +/- 0.72 nmol/mg x 5 min) in normal and Hyp mice, respectively. Km and Vmaxwere also similar in cells from the S3 segment; however, the Vmaxvalues in S3 cells in normal and Hyp mice (2.8 +/- 0.45 and 3.0 +/-0.56 nmol/mg x 5 min) were reduced in both animal models compared to those in S2 cells (P < 0.001), whereas the Km values in S3 cells from normal and Hyp mice (0.10 +/- 0.02 and 0.11 +/- 0.04 mM) wereincreased relative to those in S2 cells (P < 0.001). These data indicate that Pi transport throughout the PT of Hyp mice is intrinsically normal. Such observations exclude the presence of a nascent defect in renal Pi transport in the kidneys of Hyp mice and support the hypothesis that a humoral abnormality underlies X-linked hypophosphatemic rickets.