Impaired thrombin generation in β2-glycoprotein I null mice

Autoimmune antibodies to beta (2)-glycoprotein I (beta 2GPI) have been proposed to be clinically relevant because of their strong association with thrombosis, miscarriage, and thrombocytopenia, By using a homologous recombination approach, beta 2GPI-null mice were generated to begin to understand the physiologic and pathologic role of this prominent plasma protein in mammals. When beta 2GPI heterozygotes on a 129/Sv/C57BL/6 mixed genetic background were intercrossed, only 8.9% of the resulting 336 offspring possessed both disrupted alleles, These data suggest that beta 2GPI plays a beneficial role in implantation and/or fetal development in at least some mouse strains. Although those beta 2GPI-null mice that were born appeared to be relatively normal anatomically and histologically, subsequent analysis revealed that they possessed an impaired in vitro ability to generate thrombin relative to wild type mice. Thus, beta 2GPI also appears to play an important role in thrombin-mediated coagulation.