RENAL NA-PHOSPHATE COTRANSPORT IN MURINE X-LINKED HYPOPHOSPHATEMIC RICKETS - MOLECULAR CHARACTERIZATION()

The X-linked Hyp mouse is characterized by a specific defect in proxim al tubular phosphate (Pi) reabsorption that is associated with a decre ase in V-max of the high affinity Na+-Pi cotransport system in the ren al brush border membrane. To understand the mechanism for V-max reduct ion, we examined the effect of the Hyp mutation on renal expression of Na+-Pi cotransporter mRNA and protein. Northern hybridization of rena l RNA with a rat, renal-specific Na+-Pi cotransporter cDNA probe (NaPi -2) (Magagnin et al. 1993. Proc. Natl. Acad. Sci. USA. 90:5979-5983.) demonstrated a reduction in a 2.6-kb transcript in kidneys of Hyp mice relative to normal littermates (NaPi-2/beta-actin mRNA = 57+/-6% of n ormal in Hyp mice, n = 6, P < 0.01). N+-Pi cotransport, but not Na+-su lfate cotransport, was similar to 50% lower in Xenopus oocytes injecte d with renal mRNA extracted from Hyp mice when compared with that from normal mice. Hybrid depletion experiments documented that the mRNA-de pendent expression of Na+-Pi cotransport in oocytes was related to NaP i-2. Western analysis demonstrated that NaPi-2 protein is also signifi cantly reduced in brush border membranes of Hyp mice when compared to normals. The present data demonstrate that the specific reduction in r enal Na+-Pi cotransport in brush border membranes of Hyp mice can be a scribed to a proportionate decrease in the abundance of Na+-Pi cotrans porter mRNA and protein.