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Johnson, Theron (2006): Overexpression and characterization of hPHEX in the mouse. Dissertation, LMU München: Fakultät für Biologie



Phosphate regulating Hormone with homologies to Endopeptidases on the X- chromosome (PHEX, formerly identified as PEX) is the gene responsible for the hereditary disease X-linked hypophosphatemic rickets (XLH) and affects one in twenty thousand people, making it the most common form of rickets. A homologous disease has also been identified in Mus musculus and given the label Hyp for Hypophosphatemia. The cause of both diseases is an inactivation of the carboxy terminal end of the gene through mutation or deletion. It has been demonstrated that PHEX affects the pathway or regulatory elements for the expression of the renal sodium dependant phosphate transporter, NPT2a, and therefore phosphate resorption in the kidney. In a separate regulatory pathway PHEX affects the mineralization of osteoid, the scaffolding of hard bone. In this thesis, I have created and analyzed transgenic mouse strains overexpressing hPHEX. The transgenic animals were classified by PCR and PHEX was pinpointed by in situ hybridization to be expressed in trabecular and cortical bone as expected. Phenotypical analysis of transgenic animals demonstrated that biochemical measurements were not affected by the presence of the transgene under the control of a ubiquitous promoter. The transgenic hPHEX animals were crossed with Hyp mice to establish whether a rescue or partial rescue of the mutant phenotype was possible. Phenotypical analysis of the rescue mice indicated an improvement in body weight and bone morphology, including mineralization, over the mutant hyp mice, while most biochemical parameters remained unchanged.