Effects of Npt2 gene ablation and low-phosphate diet on renal Na(+)/phosphate cotransport and cotransporter gene expression

J Clin Invest. 1999 Sep;104(6):679-86. doi: 10.1172/JCI7103.

Abstract

The renal Na(+)/phosphate (Pi) cotransporter Npt2 is expressed in the brush border membrane (BBM) of proximal tubular cells. We examined the effect of Npt2 gene knockout on age-dependent BBM Na(+)/Pi cotransport, expression of Na(+)/Pi cotransporter genes Npt1, Glvr-1, and Ram-1, and the adaptive response to chronic Pi deprivation. Na(+)/Pi cotransport declines with age in wild-type mice (Npt2(+/+)), but not in mice homozygous for the disrupted Npt2 allele (Npt2(-/-)). At all ages, Na(+)/Pi cotransport in Npt2(-/-) mice is approximately 15% of that in Npt2(+/+) littermates. Only Npt1 mRNA abundance increases with age in Npt2(+/+) mice, whereas Npt1, Glvr-1, and Ram-1 mRNAs show an age-dependent increase in Npt2(-/-) mice. Pi deprivation significantly increases Na(+)/Pi cotransport, Npt2 protein, and mRNA in Npt2(+/+) mice. In contrast, Pi-deprived Npt2(-/-) mice fail to show the adaptive increase in transport despite exhibiting a fall in serum Pi. We conclude that (a) Npt2 is a major determinant of BBM Na(+)/Pi cotransport; (b) the age-dependent increase in Npt1, Glvr-1, and Ram-1 mRNAs in Npt2(-/-) mice is insufficient to compensate for loss of Npt2; and (c) Npt2 is essential for the adaptive BBM Na(+)/Pi cotransport response to Pi deprivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Age Factors
  • Animals
  • Biological Transport
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics*
  • Kidney / metabolism*
  • Mice
  • Mice, Knockout
  • Microvilli / metabolism
  • Phosphates / administration & dosage*
  • Phosphates / metabolism
  • RNA, Messenger / analysis
  • Sodium / metabolism*
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Phosphate Cotransporter Proteins, Type I
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • Symporters*

Substances

  • Carrier Proteins
  • Phosphates
  • RNA, Messenger
  • Slc17a1 protein, mouse
  • Slc17a2 protein, mouse
  • Slc20a1 protein, mouse
  • Slc20a2 protein, mouse
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Phosphate Cotransporter Proteins, Type I
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • Symporters
  • Sodium