Effect of age on the expression of Pex (Phex) in the mouse

Pex is a newly discovered gene (also called Phex) whose mutation is the cau se of X-linked hypophosphatemia, Other members of this gene family encode e ndopeptidases that activate or inactivate endocrine and para crine factors. Though embryonic bone expresses mRNA for the Pex gene at relatively high l evels, we have found Pex expression to be widespread in adult organs and to be poorly expressed in adult bone. This led to the hypothesis that Pex mRN A expression changes with age. To test this, genetically normal mice of the B6C3H hybrid strain were studied at 0 (newborn), 2, 3, 10, and 72 weeks of age. Organs known to express Pex were collected, and RNA was extracted fro m them. Following reverse transcription, cDNA was amplified by the polymera se chain reaction with primers for Pex and G3PDH, a housekeeping gene. The amplimers were separated by electrophoresis, blotted onto nylon membranes, and hybridized with radioactively labeled internal oligonucleotide probes. The radioactivity was quantified, and the data were analyzed as the Pex/G3P DH ratio. The brain samples had high levels of Pex mRNA expression that ros e slightly with age. Calvaria, kidney, and lung samples had the highest Per mRNA expression at birth. In these organs Pex mRNA expression fell with ag e to undetectable or barely detectable levels. Thymus, heart, and skeletal muscle samples had low Pex mRNA expression at birth that did not change wit h age. Some organs showed a decline in G3PDH levels with age, but Pcs expre ssion decreased more, leading to a reduced Pex/G3PDH ratio. The widespread expression of mRNA for Pex suggests a role beyond that of phosphate homeost asis. The high level of expression in newborn animals suggests a role in gr owth and development. This seems to occur in addition to its role for the e ndocrine regulation of phosphate homeostasis by as yet unknown humoral agen ts that must occur throughout life. In summary, Pex mRNA expression is high in brain and bone at birth. Expression remains high in brain with age but falls with age in bone, kidney, and lung.