PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of arthresbiomed central web sitesearch.manuscript submission.see also journal with issn 1478-6354registration.reference to the article.journal front page.
 
Arthritis Res. 2001; 3(Suppl A): P079.
Published online Jan 26, 2001. doi:  10.1186/ar248
PMCID: PMC3273216
Impaired in vitro thrombin generation in β2-glycoprotein I null mice
Y Sheng,1 SW Reddel,1 H Herzog,1 YX Wang,1 T Brighton,1 MP France,1 and SA Krilis1
1Department of Medicine and Department of Immunology, Allergy and Infectious Disease, University of New South Wales, The St. George Hospital, Sydney, New South Wales 2217, Australia
Supplement
21st European Workshop for Rheumatology Research
Conference
21st European Workshop for Rheumatology Research
1-4 March 2001
Vienna, Austria
Received January 15, 2001
 
β2-glycoprotein I (β2GPI) is a target antigen for 'antiphospholipid' antibodies. These antibodies are of considerable clinical importance because of their strong association with thrombosis, recurrent fetal loss, and thrombocytopenia. Although β2GPI has been shown to have a number of anticoagulant properties in vitro, its role in vivo is unknown. The aim of this study was to evaluate the function of β2GPI in vivo using a β2GPI deficient mouse model. We employed homologous recombination to disrupt the β2GPI gene in embryonic stem cells, which led to the generation of mice deficient in β2GPI. To confirm that the appropriate gene was targeted, nucleotide sequencing, map location, Northern blot analysis and Western blot analysis of the expected protein was performed. Following heterozygous () intercrosses, a total of 336 surviving offspring were genotyped. Interestingly, only 8.9% of these offspring were homozygous (-/-) for the disrupted allele, suggesting an effect on embryonic implantation or development. The remaining β2GPI-/- mice progressed normally to term and the adult mice appeared to be normal by anatomical and histological analysis. However, in vitro thrombin generation using a novel chromogenic assay demonstrated that there was a marked decrease in thrombin generation in -/- (OD405 = 0.175) compared to (OD405 = 0.312) and (OD405 = 0.576) (n = 10). This would indicate that β2GPI is likely to have a prothrombotic role in vivo. This finding is in contrast to results obtained in in vitro assay system using purified β2GPI which demonstrate anticoagulant activity for β2GPI. These knockout mice also provide a valuable in vivo model system for exploring the role of β2GPI in disease pathogenesis.
Articles from Arthritis Research are provided here courtesy of
BioMed Central