Fgf2 Conditional Knockout mouse models

Fgf2, mouse ortholog of human FGF2 and long called basic FGF, encodes a heparin-dependent ligand that activates FGFR1c and FGFR2c to drive FRS2, ERK, PI3K, and PLCgamma signaling, and it is stored bound to heparan sulfate proteoglycans in extracellular matrix, forming a mobilizable reservoir released by heparanase or injury. Translation from alternative CUG start codons yields high molecular weight isoforms that bear nuclear localization signals and act intracellularly, distinct from the classical 18 kDa form that is exported by a nonclassical, signal peptide independent route. Nulls are viable with reduced vascular tone, delayed wound healing, and neocortical neuron deficits, so constitutive deletion is feasible, but isoform-specific knockins that ablate only high molecular weight forms are far more revealing given their opposing roles in cardiac hypertrophy. Redundancy with FGF1 and other c-isoform ligands buffers single-locus loss. Use conditional alleles with Cdh5-CreER or Nestin-Cre when the endpoint is angiogenesis or neural progenitor expansion rather than systemic phenotype.

Tissue restricted knockout of Fgf2 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.