DIFFERENTIAL EXPRESSION, ABUNDANCE, AND REGULATION OF NA-PHOSPHATE COTRANSPORTER GENES IN MURINE KIDNEY()

Three classes of high-affinity Na+-P-i cotransporters are expressed in mammalian kidney. These include Npt1 (type I), Npt2 (type II), and th e cellular receptors for gibbon ape leukemia virus (Glvr-1) and amphot ropic murine retrovirus (Ram-l) (type III). We defined the tissue dist ribution as well as the relative renal abundance of Npt1, Npt2, Glvr-1 , and Ram-1 mRNAs and examined the effects of low-Pi diet, the Hyp mut ation, and growth hormone (GR) on their renal expression by ribonuclea se protection assay. In normal mouse kidney, Npt1, Npt2, Glvr-1, and R am-1 accounted for 15 +/- 1.0, 84 +/- 1.0, 0.5 +/- 0.2, and 0.5 +/- 0. 3% of total Na+-Pi cotransporter mRNAs, respectively. Evidence was obt ained for low-abundance Npt1 mRNA expression in liver and Npt2 mRNA ex pression in intestine, whereas Glvr-1 and Ram-1 mRNAs were also detect ed in bone, intestine, heart, and liver. Npt2 mRNA was localized to pr oximal tubules in the renal outer cortex, whereas Glvr-1 transcripts w ere detected throughout the kidney by in situ hybridization. The Hyp m utation elicited a significant reduction in renal Npt1 and Npt2 mRNAs (78 +/- 8 and 57 +/- 3% of normal, respectively), whereas neither low- Pi diet nor GH influenced the renal abundance of Npt1 and Npt2 transcr ipts. Renal Glvr-1 mRNA expression was significantly increased in Hyp mice and GH-treated mice (145 +/- 6 and 165 +/- 5% of control, respect ively), whereas the renal abundance of Ram-1 transcript was unaffected by either the Hyp mutation, low-P-i diet, or GH treatment. In summary , we demonstrate that Npt2 is the predominant Na+-Pi cotransporter in mouse kidney, that Npt2 and Glvr-1 have distinct patterns of renal exp ression, and that the Hyp mutation modulates the renal expression of N pt1, Npt2, and Glvr-1 mRNAs. Our results suggest that increased renal Glvr-1 mRNA may contribute to GH stimulation of renal Na+-P-i cotransp ort.