Disruption of the FGFR1-FGF23-Phosphate Axis and Targeted Therapy in a Murine Model of Osteoglophonic Dysplasia.

ABSTRACT: Osteoglophonic Dysplasia (OGD) is an autosomal dominant skeletal dysplasia characterized by impaired bone growth resulting in short stature, severe craniofacial abnormalities, and in some patients FGF23-mediated hypophosphatemia. It is caused by gain-of-function variants in FGFR1, particularly in or near the transmembrane domain of the receptor. We used CRISPR in mice to knock-in the FGFR1 p.N330I variant, chosen based on its association with FGF23 excess. Skeletal phenotyping of this Fgfr1 ^+/N330I model demonstrated markedly reduced body weight and naso-anal length, shortened long bones, and craniosynostosis, all hallmarks of the human disease. Mutant mice exhibited profound microarchitectural changes in cortical bone and severe disorganization of the growth plate

SUBMITTER: Ascone G 

PROVIDER: S-EPMC12747257 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature