Fgf1 Conditional Knockout mouse models

Fgf1, mouse ortholog of human FGF1 and historically acidic FGF, encodes the most promiscuous ligand of the family, capable of activating all seven principal FGFR splice variants when presented with heparan sulfate, which drives FRS2 recruitment, RAS to ERK signaling, PI3K, and PLCgamma output. It carries no signal peptide and exits cells by a nonclassical copper-dependent route involving S100A13 and synaptotagmin, and its intracellular pool binds FIBP and can traffic to the nucleus. Nulls are viable with only subtle vascular and wound phenotypes, making constitutive deletion straightforward, so most designs instead pursue knockins of engineered variants: thermostable or heparin-binding-deficient mutants, or receptor-biased forms that retain glucose lowering without mitogenicity, since central administration produces sustained diabetes remission. Extensive redundancy with FGF2 and other paracrine ligands at shared receptors means single-locus loss rarely produces a clean readout. Choose conditional alleles when the endpoint is tissue-autonomous repair, and humanized knockins when profiling therapeutic FGF1 analogs.

Fgf1 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.