Phosphate homeostasis is crucial for manifold physiological processes. Within the so-called bone-kidney axis, bone-derived FGF23 has emerged as the key regulator of systemic phosphate turnover. It controls, through activating FGFR/Klotho complexes in the kidney, renal phosphate handling and vitamin D metabolism. To gain a deeper insight into underlying molecular mechanisms, three different approaches were used in this thesis: (1) detection of novel candidate genes in human hypophosphatemic disorders, (2) identification of mouse models for abnormalities in bone metabolism, (3) establishment of a cell-based reporter assay to discover small-molecule regulators of FGF23 signalling.
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Phosphate homeostasis is crucial for manifold physiological processes. Within the so-called bone-kidney axis, bone-derived FGF23 has emerged as the key regulator of systemic phosphate turnover. It controls, through activating FGFR/Klotho complexes in the kidney, renal phosphate handling and vitamin D metabolism. To gain a deeper insight into underlying molecular mechanisms, three different approaches were used in this thesis: (1) detection of novel candidate genes in human hypophosphatemic disor...
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