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 beta2GPI. Although the role of beta2GPI in the pathogenesis of antiphospholipid antibody syndrome (APS) is well recognized, its exact physiological functions still remain undisclosed. Several interactions of beta2GPI with components of the coagulation cascade have been proposed, resulting in both procoagulant and anticoagulant effects. Additionally, beta2GPI 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 beta2GPI gene has been feasible. beta2GPI 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 beta2GPI are fertile, the success of early pregnancy is moderately compromised and functional beta2GPI is believed necessary for optimal implantation and placental morphogenesis.
Miyakis
Spiros
S
Department of Immunology, Allergy and Infectious Disease, St. George Hospital, University of New South Wales, Kogarah, NSW 2217, Australia.
Robertson
Sarah A
SA
Krilis
Steven A
SA
D000818:Animals; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000276:immunology; D001777:Blood Coagulation / Q000235:genetics / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000276:immunology; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I