The recently identified humanPEXgene apparently encodes for a neutral endopeptidase that is mutated in patients with X-linked hypophosphatemia. The 3′ and 5′ ends of the coding region ofPEXhave 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 mousePexgene and the demonstration of its expression in bone. MousePexcDNA is predicted to encode a protein of 749 amino acids with 95% identity to the available humanPEXsequence and significant homology to members of the membrane-bound metalloendopeptidase family. Northern blot analysis revealed a 6.6-kb transcript in bone and in cultured osteoblasts from normal mice that was not detectable in samples from theHypmouse, the murine homolog of human X-linked hypophosphatemia.Pextranscripts were, however, detectable inHypbone by RT-PCR amplification. Of particular interest, a cDNA clone from rat incisor shows 93% sequence identity to the 5′ end ofPexcDNA, suggesting thatPexmay be expressed in another calcified tissue, the tooth. The association of impaired mineralization of bone and teeth and disturbed renal phosphate reabsorption with altered expression ofPexsuggests that thePexgene product may play a critical role in these processes.