This study shows that mice homozygous for the disrupted renal sodium-phosphate (Na+-Pi) cotransporter, Npt2, (Npt2 KO) failed to show an age-dependent decrease in renal Na+-Pi cotransport or an adaptive increase in renal Na+-Pi cotransport in response to dietary Pi restriction. None of the other known renal Na+ -Pi cotransporters could compensate for the loss of Npt2. Additionally, Npt2 gene ablation resulted in a marked decrease in osteoclast number that persisted with age. Although mineral apposition rate was normal at 25- and 115-days of age in Npt2 KO mice, bone formation rate was increased at 115-days of age. These data demonstrate that Npt2 gene expression is necessary for an age-dependent decrease in renal Na+-Pi cotransport and for the renal adaptive response to dietary Pi deprivation, and that Npt2 expression is essential for normal osteoclast function and influences bone formation.

No description available.

No description available.

No description available.

No description available.

Recognising that NPT2 is the major Na/Pi cotransporter in the kidney, that hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by a renal Pi leak and, that Npt2 knockout mice demonstrate a biochemical phenotype similar to that of patients with HHRH, we sought to determine whether NPT2 was a candidate gene for this disorder. Using single-strand conformation polymorphsim (SSCP) analysis and sequencing in six unrelated pedigrees with the disease, we found no disease-causing mutations. Two polymorphisms were identified in the gene and used as markers to examine segregation of NPT2 with the disease. HHRH did not segregate with the gene markers. In addition, the impact of NPT2 on bone mineral density (BMD) was examined by genotyping a population of 104 individuals for which BMD data was available, and determining whether there was an association between NPT2 genotype and bone density. No significant association was found between NPT2 genotype and BMD.

No description available.