Fgf12 Conditional Knockout mouse models

Fgf12, ortholog of human FGF12, encodes an intracellular FGF homologous factor, formerly FHF1, that is not secreted and does not activate FGFRs; instead its beta-trefoil core binds the C-terminal tail of voltage-gated sodium channels including NaV1.5 in heart and NaV1.2 and NaV1.6 in neurons, tuning fast inactivation kinetics, promoting long-term inactivation, and shifting availability, with an alternative N-terminal isoform determining the strength of that block. Human recurrent gain-of-function variants such as the arginine to histidine substitution in the core cause developmental and epileptic encephalopathy, while other variants associate with Brugada-type conduction phenotypes, so patient-specific missense knockins are the disease-relevant allele rather than a null. Constitutive deletion is viable and yields modest excitability changes, reflecting substantial redundancy with Fgf11, Fgf13, and Fgf14 in the same compartments, so compound genetics should be planned before interpreting seizure thresholds. Match allele class to endpoint: knockin for channel biophysics and EEG phenotypes, conditional flox with neuron or cardiomyocyte Cre for compartment attribution.

Conditional deletion of Fgf12 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 Fgf12 floxed stock yields usable cohorts.