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

• Published in: Genomics (San Diego, Calif.) Vol. 36; no. 1; pp. 22 - 28
• Main Authors: DU, L, DESBARATS, M, VIEL, J, GLORIEUX, F. H, CAWTHORN, C, ECAROT, B
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 15-08-1996
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Bone and Bones - chemistry; Classical genetics, quantitative genetics, hybrids; Cloning, Molecular; DNA Mutational Analysis; DNA, Complementary - genetics; Endopeptidases - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; Genetic Linkage; Genetics of eukaryotes. Biological and molecular evolution; Hypophosphatemia, Familial - genetics; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Organ Specificity; Osteoblasts - chemistry; PHEX Phosphate Regulating Neutral Endopeptidase; Proteins - genetics; RNA, Messenger - analysis; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Vertebrata; X Chromosome; Sex linked character; Animal model; Hydroelectrolytic balance disorder; Nucleotide sequence; Enzyme; Rodentia; Homology; Metalloendopeptidases; Phosphorus; Gene expression; Inorganic element; Genetic disease; Metabolic disorder; Vertebrata; Mammalia; Complementary DNA; Mouse; Endopeptidase; Hydrolases; Genetics; Hypophosphatemia; Bone; Proteinases
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1996.0421

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. Mouse Pex cDNA is predicted to encode a protein of 749 amino acids with 95% identity to the available human PEX sequence 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 the Hyp mouse, the murine homolog of human X-linked hypophosphatemia. Pex transcripts were, however, detectable in Hyp bone by RT-PCR amplification. Of particular interest, a cDNA clone from rat incisor shows 93% sequence identity to the 5' end of Pex cDNA, suggesting that Pex may 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 of Pex suggests that the Pex gene product may play a critical role in these processes.