F10 Conditional Knockout mouse models

F10 encodes coagulation factor X, the mouse ortholog of human F10 and the convergence point of the intrinsic and extrinsic cascades. The vitamin K dependent zymogen carries an amino-terminal Gla domain whose gamma-carboxyglutamate residues mediate calcium-dependent phospholipid binding, two EGF-like modules, and a trypsin-like protease domain; activation by the tissue factor and factor VIIa complex or by the factor IXa and factor VIIIa intrinsic tenase generates factor Xa, which assembles with factor Va on activated platelet membranes into prothrombinase to convert prothrombin to thrombin, and is checked by antithrombin and tissue factor pathway inhibitor. Complete deficiency is not survivable in mouse, causing embryonic and perinatal lethality from hemorrhage, so hypomorphic or conditional alleles are required for adult phenotyping. Low-expressing knockins that titrate factor X to a few percent of normal are the established route for bleeding and thrombosis endpoints, whereas humanized knockins suit direct oral anticoagulant and reversal agent pharmacology.

Tissue restricted knockout of F10 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.