Ka. Hruska et al., X-LINKED HYPOPHOSPHATEMIC RICKETS AND THE MURINE HYP HOMOLOG, American journal of physiology. Renal, fluid and electrolyte physiology, 37(3), 1995, pp. 357-362
Recent studies have reported the cloning of several sodium-dependent p
hosphate cotransport proteins from the apical membrane of proximal tub
ules of several species. The human proximal tubule apical sodium-phosp
hate cotransport protein maps to chromosome 5 in the 5q35 region, indi
cating that this gene is not a candidate for the genetic defect leadin
g to X-Linked hypophosphatemia (XLH). Studies in what is thought to be
the murine XLH homologue, Hyp, also indicate that the proximal tubula
r phosphate cotransporter gene does not map to the X chromosome. In Hy
p, message levels for the apical membrane sodium cotransport protein a
re reduced by similar to 50%, similar to the reductions in the apical
membrane protein levels of the transporter. This indicates a potential
transcriptional defect in Hyp, leading to underexpression of the sodi
um-dependent phosphate transport protein. Recent studies in the Hyp os
teoblast have characterized the intrinsic abnormalities of the cell le
ading to the osteomalacia characteristic of both Hyp and XLH. These st
udies demonstrate that the Hyp osteoblast expresses normal rates of ph
osphate transport, but altered gluconeogenesis similar to the proximal
tubule, and that there is an underphosphorylation of an important mat
rix protein, osteopontin. Since osteopontin is involved in matrix mine
ralization, defective posttranslational modification of the protein co
uld be a factor in producing the osteomalacia of the Hyp. Other recent
studies have demonstrated improved modalities of treatment for Hyp an
d potentially for XLH. These involve the use of phosphate and nonhyper
calcemic analogues of 1 alpha,25-dihydroxyvitamin D-3. Thus, although
the detection of the genetic defect producing XLH and Hyp is awaited,
significant advances in the characterization of the phenotype and the
bone abnormalities continue.