PEX PEX TISSUE DISTRIBUTION AND EVIDENCE FOR A DELETION IN THE 3'-REGION OF THE PEX GENE IN X-LINKED HYPOPHOSPHATEMIC MICE/

PEX, a phosphate-regulating gene with homology to endopeptidases on th e X chromosome, was recently identified as the candidate gene for X-li nked hypophosphatemia. In the present study, we cloned mouse and human Pex/PEX cDNAs encoding part of the 5' untranslated region, the protei n coding region, and the entire 3' untranslated region, determined the tissue distribution of Pex/PEX mRNA, and characterized the Per mutati on in the murine Hyp homologue of the human disease. Using the reverse transcriptase/polymerase chain reaction (RT/PCR) and ribonuclease pro tection assays, we found that Pex/PEX mRNA is expressed predominantly in human fetal and adult mouse calvaria and long bone. With RNA from H yp mouse bone, an RT/PCR product was generated with 5' but not 3' Per primer pairs and a protected Per mRNA fragment was detected with 5' bu t not 3' Per riboprobes by ribonuclease protection assay, Analysis of the RT/PCR product derived from Hyp bone RNA revealed an aberrant Per transcript with retention of intron sequence downstream from nucleotid e 1302 of the Per cDNA. Per mRNA was not detected on Northern blots of poly (A)(+) RNA from Hyp bone, while a low-abundance Per transcript o f approximate to 7 kb was apparent in normal bone. Southern analysis o f genomic DNA from Hyp mice revealed the absence of hybridizing bands with cDNA probes from the 3' region of the Per cDNA. We conclude that Pex/PEX is a low-abundance transcript that is expressed predominantly in bone of mice and humans and that a large deletion in the 3' region of the Pex gene is present in the murine Hyp homologue of X-linked hyp ophosphatemia.