Effects of Npt2 gene ablation and low-phosphate diet on renal Na+/phosphate cotransport and cotransporter gene expression
Hannah M. Hoag, … , Claude Gauthier, Harriet S. Tenenhouse
Hannah M. Hoag, … , Claude Gauthier, Harriet S. Tenenhouse
Published September 15, 1999
Citation Information: J Clin Invest. 1999;104(6):679-686. https://doi.org/10.1172/JCI7103.
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Article

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

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.

Authors

Hannah M. Hoag, Josée Martel, Claude Gauthier, Harriet S. Tenenhouse

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Figure 2

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Effect of Npt2 gene knockout and age on renal BBM Npt2 and meprin immuno...
Effect of Npt2 gene knockout and age on renal BBM Npt2 and meprin immunoreactive protein. BBM proteins, prepared from Npt2+/+ mice at 21, 45, and 115 days of age and from 115-day-old Npt2–/– mice, were fractionated on 10% SDS-PAGE gels, transferred to nitrocellulose membranes, and probed with a rabbit polyclonal anti-rat Npt2 antibody and an mAb raised against the α subunit of rat meprin. Bands depicting Npt2 (83 kDa) and meprin (65 kDa) immunoreactive proteins are indicated by arrows. The figure depicts 1 of 3 BBM preparations per group.