Fgfr2 Conditional Knockout mouse models

Fgfr2, the mouse ortholog of human FGFR2, encodes an FGF receptor whose biology is dominated by mutually exclusive splicing of exons encoding the second half of Ig domain III, producing FGFR2 IIIb in epithelium, which responds to FGF7 and FGF10 from mesenchyme, and FGFR2 IIIc in mesenchyme, which responds to epithelial FGF2, FGF8 and FGF9, establishing the reciprocal epithelial-mesenchymal loop that patterns limb, lung and craniofacial structures. Craniosynostosis alleles including S252W and P253W in Apert syndrome and cysteine substitutions in Crouzon syndrome act by broadening ligand specificity or promoting ligand-independent disulfide dimerization, while FGFR2 amplification and fusions drive gastric and intrahepatic cholangiocarcinoma. Because a conventional null is embryonic lethal from limb bud and placental failure, and because isoform-specific alleles produce entirely different phenotypes, splice-restricted alleles are the sharpest tool available. Fgfr1 and Fgfr3 compensate in skeletal contexts. Choose isoform-specific nulls for developmental patterning and conditional activating knockins for FGFR inhibitor response and resistance studies.

Tissue restricted knockout of Fgfr2 keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.