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 beta(2)GPL Although the role of beta(2)GPI in the pathogenesis of antiphospholipid antibody syndrome (APS) is well recognized, its exact physiological functions still remain undisclosed. Several interactions of beta(2)GPI with components of the coagulation cascade have been proposed, resulting in both procoagulant and anticoagulant effects. Additionally, beta(2)GPI 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 beta(2)GPI gene has been feasible. beta(2)GPI 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 beta(2)GPI are fertile, the success of early pregnancy is moderately compromised and functional beta(2)GPI is believed necessary for optimal implantation and placental morphogenesis. (C) 2004 Published by Elsevier Inc.