Fgf23 Conditional Knockout mouse models

Fgf23, mouse ortholog of human FGF23, encodes the osteocyte and osteoblast derived endocrine regulator of phosphate homeostasis, a ligand with weak heparan sulfate binding that requires alpha-Klotho as coreceptor with FGFR1c on renal proximal tubule and parathyroid cells to suppress the sodium phosphate cotransporters NPT2a and NPT2c and to downregulate CYP27B1 while inducing CYP24A1, thereby lowering serum phosphate and active vitamin D. Bioactivity is set by furin-family cleavage at an RXXR motif that is itself blocked by GALNT3-dependent O-glycosylation, so autosomal dominant hypophosphatemic rickets arises from cleavage-resistant arginine substitutions while familial tumoral calcinosis arises from failed glycosylation or loss of function. Nulls are viable but hyperphosphatemic with ectopic calcification and short lifespan. Allele choice follows disease logic precisely: cleavage-resistant knockins model excess and reproduce XLH-like phenotypes seen with Phex loss, floxed conditionals localize the osteocyte source, and humanized knockins are required for burosumab and other antibody testing against phosphate, ALP, and rickets scoring endpoints.

Conditional deletion of Fgf23 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Fgf23 floxed stock yields usable cohorts.