Sodium-phosphate transporter adaptation to dietary phosphate deprivation in normal and hypophosphatemic mice

J. F. Collins, N. Bulus, F. K. Ghishan

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 Pi 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 (~ 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. We conclude that the upregulation in renal Na+-P(i) transporter activity induced by Pi deprivation in both normal and Hyp mice is the result of an increased mRNA level encoding the Na+-P(i) transporter, which leads to increased amounts of immunoreactive and functional protein.

Original languageEnglish (US)
Pages (from-to)G917-G924
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume268
Issue number6 31-6
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • hypophosphatemic vitamin D-resistant rickets
  • sodium-phosphate transporter message levels
  • sodium-phosphate transporter protein levels

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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