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Impaired thrombin generation in beta 2-glycoprotein I null mice


Autoimmune antibodies to beta(2)-glycoprotein I (beta2GPI) have been proposed to be clinically relevant because of their strong association with thrombosis, miscarriage, and thrombocytopenia. By using a homologous recombination approach, beta2GPI-null mice were generated to begin to understand the physiologic and pathologic role of this prominent plasma protein in mammals. When beta2GPI 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 beta2GPI plays a beneficial role in implantation and/or fetal development in at least some mouse strains. Although those beta2GPI-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, beta2GPI also appears to play an important role in thrombin-mediated coagulation.

Type Journal
ISBN 0021-9258 (Print)
Authors Sheng, Y.;Reddel, S. W.;Herzog, H.;Wang, Y. X.;Brighton, T.;France, M. P.;Robertson, S. A.;Krilis, S. A. :
Garvan Authors Prof Herbert Herzog
Publisher Name J BIOL CHEM
Published Date 2001-01-01 00:00:00
Published Volume 276
Published Issue 17
Published Pages 13817-21
Status Published In-print