Renal expression of Na+-phosphate cotransporter mRNA and protein: effect of the Gy mutation and low phosphate diet.
The X-linked Gy mutation is closely linked, but not allelic, to Hyp and is characterized by rickets, hypophosphatemia, decreased renal tubular maximum for phosphate (Pi) reabsorption (TmP) and a specific reduction in renal brush-border membrane (BBM) Na+-Pi cotransport. Gy mice, like their normal littermates, respond to a low-Pi diet with an increase in BBM Na+-Pi cotransport, but fail to show an adaptive increase in Tmp. Using an antibody raised against the NH2 terminal peptide of the rat renal-specific Na+-Pi cotransporter (NaPi-2) and a NaPi-2 cDNA probe, we examined the effect of the Gy mutation and low-Pi diet (0.03% Pi) on NaPi-2 protein and mRNA abundance. The reduction in BBM Na+-Pi cotransport in Gy mice (51 +/- 5% of normal, P < 0.05) was associated with a decrease in NaPi-2 protein (46 +/- 12% of normal, P < 0.05) and mRNA abundance (76 +/- 5%, P < 0.05). The low-Pi diet elicited a two- to three-fold increase in Na+-Pi cotransport in both normal and Gy mice that was accompanied by a large increase in NaPi-2 protein (10.2-fold in normal and 16.9-fold in Gy mice) and a modest increase in NaPi-2 mRNA (1.3-fold in both mouse strains, P < 0.05). The present data demonstrate that (1) the renal defect in BBM Pi transport in Gy mice can be ascribed to a deficit in NaPi-2 protein and mRNA abundance, (2) both normal and Gy mice respond to low Pi with an adaptive increase in NaPi-2 protein that exceeds the increase in Na+-Pi cotransport activity and NaPi-2 mRNA, (3) the adaptive increase in NaPi-2 protein and mRNA are not sufficient for the overall increase in TmP following Pi restriction.
Beck
L
L
Department of Pediatrics and Human Genetics, McGill University, Montreal, Canada H3H 1P3
Tenenhouse
H S
HS
Meyer
R A
RA
Meyer
M H
MH
Biber
J
J
Murer
H
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D017136:Ion Transport; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010710:Phosphates / Q000008:administration & dosage* / Q000378:metabolism*; D016226:Phosphorus, Dietary / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D012279:Rickets / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014960:X Chromosome / Q000235:genetics
D002352:Carrier Proteins; D010710:Phosphates; D016226:Phosphorus, Dietary; D012333:RNA, Messenger; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D012964:Sodium