Decreased transcription of the sodium-phosphate transporter gene in the hypophosphatemic mouse.
Recently, it has been hypothesized that the proximal tubular Na(+)-Pi transporter may play a role in murine X-linked hypophosphatemic vitamin D-resistant rickets. In the present investigation, Western blot analysis of renal brush-border membrane proteins, utilizing polyclonal antisera raised against the mouse Na(+)-Pi transporter, revealed a predominant band at 87 kDa in normal and hypophosphatemic (Hyp) mice. The intensity of this band was reduced in the Hyp mouse by 4.5-fold (Hyp/normal = 0.22 +/- 0.04, n = 3, P < 0.05). Additionally, immunohistochemical analysis of kidney cortex in both mice localized the protein to the apical membrane of the proximal tubules. Relative transcription rates of the Na(+)-Pi transporter gene in the normal and Hyp mouse were then investigated. Nuclear run-on assays showed a 51 +/- 0.02% decreased rate of transcription of the Na(+)-Pi transporter gene in the Hyp mice (n = 3). Thus abnormal transcriptional control of this gene in the Hyp mouse likely plays a role in X-linked hypophosphatemia.
Collins
J F
JF
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2576, USA.
Scheving
L A
LA
Ghishan
F K
FK
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005796:Genes; D017674:Hypophosphatemia / Q000235:genetics*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000378:metabolism; D014176:Protein Biosynthesis; D012016:Reference Values; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014018:Tissue Distribution; D014158:Transcription, Genetic
D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters