Fgf18 Conditional Knockout, Knockout mouse models

Why model Fgf18

Fgf18, ortholog of human FGF18, encodes a secreted FGF8 subfamily ligand that signals principally through FGFR3c and FGFR4, with additional FGFR1c and FGFR2c engagement, and functions as a positive regulator of chondrocyte proliferation, matrix production, and growth plate hypertrophic transition while simultaneously restraining osteoblast differentiation timing, thereby coordinating endochondral ossification and cranial suture closure. It is the basis of the intra-articular cartilage anabolic agent sprifermin, which makes species-matched receptor engagement a practical concern. Germline nulls die in the perinatal period with delayed ossification, expanded proliferative zones, and craniosynostosis-like suture abnormalities, so conditional floxed alleles combined with Col2a1-Cre, Prrx1-Cre, or Sp7-Cre are the appropriate tool for postnatal joint and skeletal work. Overlapping activity from Fgf9 at the same c-isoform receptors means compound conditionals are advisable when the endpoint is complete growth plate FGF input. Align allele class to readout: humanized knockins for sprifermin-type pharmacology, conditional deletion for cartilage homeostasis and osteoarthritis progression.