Genetic Ablation of Sfrp4 in Mice Does Not Affect Serum Phosphate Homeostasis

Serum phosphate levels are regulated by PTH and the fibroblast growth factor 23 (Fgf23)/Klotho endocrine system, which both affect expression of Npt2a and thus the apical reabsorption of phosphate in the proximal renal tubules. In addition to Fgf23, secreted frizzled-related protein 4 (Sfrp4) has recently been implicated as an additional phosphate regulator in vivo and in vitro. Here we demonstrate that ablation of the Sfrp4 gene in mice does not lead to altered serum or urine phosphate levels. Furthermore, Sfrp4 is unable to compensate for the absence of Fgf23 or Klotho because double knockouts have a similar biochemical profile and phenotype as animals with ablation of Fgf23 or Klotho alone. Taken together, our data suggest that Sfrp4 does not contribute to the long-term regulation of serum phosphate levels in mice. (Endocrinology 152: 2031-2036, 2011)