The renal sodium-phosphate transporter and X-linked hypophosphatemic vitamin D-resistant rickets

• Published in: Nutrition Research 1996-05, Vol.16 (5), p.881-898
• Main Authors: Collins, James F., Ghishan, Fayez K.
• Format: Article
• Language: English
• Subjects: ABSORCION DE SUSTANCIAS NUTRITIVAS; ABSORPTION DE SUBSTANCES NUTRITIVES; ANION; ANIONES; Biological and medical sciences; CLONACION; CLONAGE; DIETA; Endocrinopathies; EPITELIO; EPITHELIUM; EXPRESION GENICA; EXPRESSION DES GENES; FOSFATOS; GENOTIPOS; GENOTYPE; HIPOFOSFATEMIA; Hyp mouse; Hypophosphatemic rickets; HYPOPHOSPHATEMIE; ION; IONES; Kidney; Medical sciences; MODELE ANIMAL; MODELOS ANIMALES; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases); PHOSPHATE; PROTEINAS; PROTEINE; RACHITISME; RAQUITISMO; RATON; REGIME ALIMENTAIRE; SODIO; SODIUM; Sodium-phosphate transporter; SOURIS
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/0271-5317(96)00081-4

The sodium-phosphate ( Na + P i ) transporter is a brush-border membrane specific protein located in the epithelia of the kidney and intestine of mammals. This transporter is involved in the pathogenesis of X-linked hypophosphatemic rickets. X-linked hypophosphatemic vitamin D-resistant rickets is the most common form of rickets in man, and is characterized by low serum phosphate levels. The ( Hyp) mouse is thought to be an animal homologue of this disease in humans. Decreased renal proximal tubular reabsorption of phosphate has been observed in the ( Hyp) mouse, resulting in hyperphosphaturia. The Na + P i ) transporter was cloned from the mouse, and cRNA generated from this cDNA showed increased sodium-dependent phosphate uptake in Xenopus oocytes. Northern blot analysis showed recognition of three transcripts in normal and ( Hyp) mice at 2.6, 4.6, and 10 kilobases, with all three bands being decreased in the ( Hyp) mouse. In-situ hybridization localized the message to the renal proximal tubules in both mice. Polyclonal antiserum, raised against a C-terminal synthetic peptide specific for this transporter, recognized several bands at 152, 87, 82, 77, and 37 kDa on Western blots of renal brush-border membrane proteins from both mice. The intensity of all bands was decreased in the ( Hyp) mouse samples by 5–10 fold. Immunohistochemistry localized the immunoreactive protein to the apical membrane of the proximal tubules in both mice. The transcription rate of this gene was decreased by 2-fold in the ( Hyp) mouse. Dietary phosphate deprivation resulted in increased transporter activity, message levels, and immunoreactive protein levels in both ( Hyp) and control mice. Cloning of the PEX gene (from the Hyp) locus on chromosome X of patients with hypophosphatemic rickets would suggest that a product of the PEX gene alters the function of the Na + P i ) transporter.