,67,69 Spontaneous truncating mutations identified in mice led to the discovery and widespread use of the Hyp (PhexHyp) mouse, which phenocopies XLH in humans (In humans, inactivating mutations in the PHEX gene decrease the enzymatic activity of PHEX, resulting in dramatic elevations in FGF23, a critical hormone regulating phosphate homeostasis in the kidney.70 This evidence concerns the gene PHEX and X-linked dominant hypophosphatemic rickets.