F12 Conditional Knockout mouse models

F12 encodes factor XII (Hageman factor), the mouse ortholog of human F12, a zymogen with fibronectin type I and II, EGF, and kringle domains plus a proline-rich region that autoactivates upon contact with polyanionic surfaces including polyphosphate, misfolded protein aggregates, collagen, and artificial materials. Factor XIIa then cleaves prekallikrein to plasma kallikrein, which reciprocally amplifies factor XII activation and liberates bradykinin from high molecular weight kininogen, and it activates factor XI to feed intrinsic coagulation. This dual output makes F12 the entry point for both contact-driven thrombosis and kinin-mediated vascular permeability, with human gain-of-function variants such as Thr309Lys causing hereditary angioedema despite normal C1 inhibitor. Nulls display normal hemostasis yet are protected in arterial thrombosis and stroke models, precisely the dissociation of interest. Knockins of angioedema-associated alleles are the design for permeability and attack-driven endpoints, whereas humanization supports antibody and antisense programs directed at human factor XII.

Tissue restricted knockout of F12 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.