Mepe, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone.

The MEPE (matrix extracellular phosphoglycoprotein) gene is a strong candidate for the tumor-derived phosphaturic factor in oncogenic hypophosphatemic osteomalacia (OHO). X-linked hypophosphatemia (XLH) is phenotypically similar to OHO and results from mutations in PHEX, a putative metallopeptidase believed to process a factor(s) regulating bone mineralization and renal phosphate reabsorption. Here we report the isolation of the murine homologue of MEPE, from a bone cDNA library, that encodes a protein of 433 amino acids, 92 amino acids shorter than human MEPE.

1,25-(OH)2D3 down-regulates expression of Phex, a marker of the mature osteoblast.

Mutations in the PHEX/Phex gene, which encodes for a protein with homology to neutral endopeptidases, are responsible for human and murine X-linked hypophosphatemia. The present study examined Phex messenger RNA (mRNA) and protein expression in cultured osteoblasts and its regulation by 1,25-(OH)2D3. Phex mRNA levels were quantitated on Northern blots by densitometric analysis relatively to GAPDH mRNA levels.

cDNA cloning of the murine Pex gene implicated in X-linked hypophosphatemia and evidence for expression in bone.

The recently identified human PEX gene apparently encodes for a neutral endopeptidase that is mutated in patients with X-linked hypophosphatemia. The 3' and 5' ends of the coding region of PEX have not been cloned, nor has the tissue expression of the gene been identified. Here we report the isolation and characterization of the complete open reading frame of the mouse Pex gene and the demonstration of its expression in bone.

Fine genetic mapping of the Hyp mutation on mouse chromosome X.

The hypophosphatemic (Hyp) mouse is the murine homolog of hypophosphatemic vitamin-D-resistant rickets (HYP) in human. Despite extensive investigations in the Hyp mouse, the pathophysiology of this X-linked dominant disorder remains unclear. As a first step toward cloning the Hyp gene, we have generated a high-resolution linkage map in the vicinity of the Hyp locus using two independent backcross panels segregating the Hyp mutation, one generated from an interspecific mating between C57BL/6J-Hyp/Hyp and Mus spretus and the other from an intrasubspecific mating between C57BL/6J-Hyp/Hyp and Mus musculus castaneus.