Beta-2 glycoprotein I and its role in antiphospholipid syndrome—lessons from knockout mice

The antiphospholipid syndrome is characterized by the presence in serum of autoantibodies against β2GPI. Although the role of β2GPI in the pathogenesis of antiphospholipid antibody syndrome (APS) is well recognized, its exact physiological functions still remain undisclosed. Several interactions of β2GPI with components of the coagulation cascade have been proposed, resulting in both procoagulant and anticoagulant effects. Additionally, β2GPI has been implicated in the mechanism of recurrent fetal loss entailed in APS. Recently, using a homologous recombination approach, reproduction of mice homozygous for deletion of the β2GPI gene has been feasible. β2GPI knockout mice offer a valuable tool for revealing the physiological role of the protein. These mice show decreased in vitro ability for thrombin generation. Furthermore, although mice lacking β2GPI are fertile, the success of early pregnancy is moderately compromised and functional β2GPI is believed necessary for optimal implantation and placental morphogenesis.