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 neutra l endopeptidase that is mutated in patients with X-linked hypophosphat emia. The 3' and 5' ends of the coding region of PEX have not been clo ned, nor has the tissue expression of the gene been identified. Here w e report the isolation and characterization of the complete open readi ng frame of the mouse Pex gene and the demonstration of its expression in bone. Mouse Pex cDNA is predicted to encode a protein of 749 amino acids with 95% identity to the available human PEX sequence and signi ficant homology to members of the membrane-bound metalloendopeptidase family. Northern blot analysis revealed a 6.6-kb transcript in bone an d in cultured osteoblasts from normal mice that was not detectable in samples from the Hyp mouse, the murine homolog of human X-linked hypop hosphatemia. Pex transcripts were, however, detectable in Hyp bone by RT-PCR amplification, Of particular interest, a cDNA clone from rat in cisor shows 93% sequence identity to the 5' end of Pex cDNA, suggestin g that Pex may be expressed in another calcified tissue, the tooth. Th e association of impaired mineralization of bone and teeth and disturb ed renal phosphate reabsorption with altered expression of Pex suggest s that the Pex gene product may play a critical role in these processe s. (C) 1996 Academic Press, Inc.