Review of recent papers on XLH

What we knew before

- FGF23 is a secreted protein with phosphaturic activity.

- FGF23 is elevated in XLH and HYP mice.

- Primary cause of XLH is a mutation in PHEX

- Links btw PHEX and FGF23 are still unclear

What they have done

- They created a new Hyp mouse line with the FGF23 gene replaced by a gene coding for a fluorescent protein (eGFP) to obtain a combined PHES and FGF23 deficiency.

- In this model, the activation of the fgf23 expression leads to the accumulation of this protein, which is easily detected.

What we learn from this study

- FGF23 is not only expressed in osteocytes (bones) but also in thymus or endothelial cells of bone marrow.

- PHEX inactivation leads to the activation of FGF23 in osteocytes only.

- PHEX is probably acting upstream of FGF23 in the development of hypophosphatemia and mineralization defects.

- This suggests that there is still unknown factor (or Phex substrate) that is acting downstream of PHEX and regulate the expression of FGF23.