Sodium-phosphate transporter adaptation to dietary phosphate deprivation in normal and hypophosphatemic mice.
The X-linked hypophosphatemic (Hyp) mouse is a model for hypophosphatemic vitamin D-resistant rickets and is a homologue of human X-linked hypophosphatemia. The defect in the Hyp mouse appears to be related to decreased renal tubular reabsorption of P(i) via the renal brush-border membrane (Na(+)-P(i)) transporter. Dietary P(i) deprivation upregulates Na(+)-P(i) transport activity in brush-border membrane vesicles (BBMV) isolated from both normal and Hyp mice; however, the molecular mechanisms underlying this phenomenon are not known. The current studies were designed to investigate the effect of P(i) deprivation on the renal Na(+)-P(i) transporter. Low P(i) diet upregulated Na(+)-P(i) transporter activity in isolated BBMV by 2.1-fold in normal and Hyp mice (n = 3, P = 0.01). Low P(i) diet also induced a 1.9 +/- 0.3-fold increase in normal mice and 2.9 +/- 0.4-fold increase in Hyp mice in Na(+)-P(i) transporter message levels (n = 3, P = 0.028). The increase in message level encoding the Na(+)-P(i) transporter stimulated increased Na(+)-dependent P(i) uptake by Xenopus laevis oocytes when poly(A)+ RNA was injected into them from mice on low P(i) diet (approximately 1.67-fold in normal mice and 1.33-fold in Hyp mice). Immunoreactive protein levels increased 2.3 +/- 0.4-fold in normal mice and 8.2 +/- 0.5 in the Hyp mouse kidney cortexes (n = 3, P = 0.0001) in response to dietary P(i) deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Collins
J F
JF
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2576, USA.
Bulus
N
N
Ghishan
F K
FK
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D017674:Hypophosphatemia / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008871:Microvilli / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010710:Phosphates / Q000378:metabolism; D016226:Phosphorus, Dietary / Q000494:pharmacology*; D012016:Reference Values; D012279:Rickets / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D000906:Antibodies; D002352:Carrier Proteins; D010455:Peptides; D010710:Phosphates; D016226:Phosphorus, Dietary; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters