Phex cDNA cloning from rat bone and studies on phex mRNA expression: tissue-specificity, age-dependency, and...

Phosphate regulating gene with homology to endopeptidases on the X chromosome (Phex) inactivating mutations cause X-linked hypophosphatemia (XLH). The disorder is characterized by decreased renal phosphate (Pi) reabsorption in both humans and mice, in the latter shown to be due to a reduction in mRNA and protein of type II sodium-dependent phosphate cotransporter (NadPi-II). To gain insight into the physiological role of Phex, we cloned the rat cDNA and examined tissue-specific and age-dependent mRNA expression. The rat full-length cDNA (2247 nucleotides) shares 96 and 90% identity with the mouse and human cDNA, respectively. We found 6.6 kb Phex transcripts in calvarial bone and lungs, and a weaker signal in liver of newborn rats. In adult animals, Phex mRNA signals were weaker in bone and lungs and absent in liver. Phex mRNA expression in bones and NadPi-I and -II cotransporter mRNA expression in kidney were also determined in hypophysectomized rats. These rats, which lack GH and IGF I, stop growing and exhibit decreased serum Pi levels. Treatment during 6 days with IGF I stimulated growth and increased serum Pi. Phex and NadPi-II cotransporter mRNA levels were higher in IGF I than in vehicle-treated animals, while mRNA expression of NadPi-I, 1alpha-hydroxylase and 24-hydroxylase and serum levels of calcitriol remained unaffected. Age-dependency of Phex expression suggests a role for Phex in Pi retention during growth. Moreover, our findings indicate that an increase in Phex expression in bones under the influence of IGF I may contribute to increased serum Pi by enhancing renal phosphate reabsorption. Because IGF I treatment increased NadPi-II mRNA expression and serum Pi, IGF I appears to act at least partially at pretranslational levels to increase NadPi-II mediated renal Pi retention in growing rats.