Overexpression and characterization of hPHEX in the mouse

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.