Effects of Npt2 gene ablation and low-phosphate diet on renal Na(+)/phosphate cotransport and cotransporter gene expression.
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.
Hoag
H M
HM
Department of Biology, Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Montreal, Quebec H3H 1P3, Canada.
Martel
J
J
Gauthier
C
C
Tenenhouse
H S
HS
D000222:Adaptation, Physiological; D000367:Age Factors; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000008:administration & dosage* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012964:Sodium / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters
D002352:Carrier Proteins; D010710:Phosphates; D012333:RNA, Messenger; C493547:Slc17a1 protein, mouse; C493549:Slc17a2 protein, mouse; C493587:Slc20a1 protein, mouse; C493565:Slc20a2 protein, mouse; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; D012964:Sodium