Sodium-phosphate transport in the kidney and intestine of the hypophosphatemic mouse.
X-linked hypophosphatemic vitamin D-resistant rickets is the most common inherited form of vitamin D-resistant rickets in man. The current studies were designed to characterize the defect in the sodium (Na+)-phosphate transporter in the (Hyp) mouse model. The slope of initial rate of phosphate uptake was significantly decreased in the kidney but not in intestinal brush border membranes of the (Hyp) mice compared with genetically matched controls. Phosphate uptake by the basolateral membranes of the intestine and kidney was similar in the (Hyp) and control mice. Kinetic analysis of phosphate uptake by renal brush border membranes showed a Vmax of 0.32 +/- 0.06 and 1.6 +/- 0.1 nmol/mg protein per 15 s (P < 0.01) and Km of 0.07 +/- 0.06 and 0.39 +/- 0.05 mM in (Hyp) and control mice respectively (P < 0.05). Vmax and Kmax of jejunal uptake of phosphate were similar in (Hyp) and control mice. To confirm these findings, we expressed the Na(+)-phosphate transporter in Xenopus laevis oocytes. Na(+)-dependent phosphate uptake in the oocytes was expressed 6 days after renal and intestinal poly(A)+ RNA injection, however, uptake values were significantly lower in oocytes injected with renal poly(A)+ RNA from the (Hyp) mice compared with controls (P < 0.01). No differences were noted in phosphate uptake by oocytes injected with poly(A)+ RNA from the jejunum of the (Hyp) or control mice. These studies suggest that the defect in the (Hyp) mice is localized to the kidney and is secondary to diminished activity and/or function of the Na(+)-phosphate transporter.
Nakagawa
N
N
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2576.
Ghishan
F K
FK
D000818:Animals; D001693:Biological Transport, Active; D015415:Biomarkers; D007015:Hypophosphatemia, Familial / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D012964:Sodium / Q000378:metabolism*; D014982:Xenopus laevis
D015415:Biomarkers; D010710:Phosphates; D011061:Poly A; D012313:RNA; D012964:Sodium