Mutations in the PHEX gene are responsible for X-linked hypophosphatemia, the most prevalent form of inherited rickets in humans. PHEX is an endopeptidase that is expressed in bone and parathyroid gland and shown to cleave parathyroid hormone [PTH]. To determine whether PHEX is regulated by PTH we used two models: (1) 5/6 nephrectomized [5/6 Nx] rats which exhibit significant hyperparathyroidism and (2) 1,25-dihydroxyvitamin D3 [1,25(OH)2D]-treated rats, which are characterized by marked hypoparathyroidism. We demonstrate that 5/6 Nx elicits an increase in PHEX mRNA and protein abundance in rat tibia whereas 1,25(OH)2D causes a decrease in both tibial parameters. In addition, administration of 1,25(OH)2D to 5/6 Nx rats blunts the increase in PHEX gene expression in bone. We also observe a significant correlation between serum PTH concentration and tibial PHEX expression. Our data thus provides evidence for a role of PTH in the regulation of PHEX expression.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.78328 |
| Date | January 2002 |
| Creators | Brewer, Angela |
| Contributors | Tenenhouse, H. S. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001974440, proquestno: AAIMQ88163, Theses scanned by UMI/ProQuest. |
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