First Author | Hoag HM | Year | 1999 |
Journal | J Clin Invest | Volume | 104 |
Issue | 6 | Pages | 679-86 |
PubMed ID | 10491403 | Mgi Jnum | J:110765 |
Mgi Id | MGI:3641022 | Doi | 10.1172/JCI7103 |
Citation | Hoag HM, et al. (1999) Effects of Npt2 gene ablation and low-phosphate diet on renal Na(+)/phosphate cotransport and cotransporter gene expression. J Clin Invest 104(6):679-86 |
abstractText | 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. |