Impaired thrombin generation in beta(2)-glycoprotein I null mice

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