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J. Biol. Chem., Vol. 276, Issue 17, 13817-13821, April 27, 2001
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From the Autoimmune antibodies to
Impaired Thrombin Generation in
2-Glycoprotein I
Null Mice*
,,,
,
Department of Medicine and the Department of
Immunology, Allergy, and Infectious Disease, and the
¶ Department of Haematology, University of New South Wales, The
St. George Hospital, Sydney, New South Wales 2217, § Garvan Institute of Medical Research, St. Vincent's
Hospital, Darlinghurst, New South Wales 2010, the
Department of Veterinary Anatomy and Pathology, the University
of Sydney, Sydney, New South Wales 2006, and the ** Department of
Obstetrics and Gynaecology and Reproductive Medicine Unit, Adelaide
University, Adelaide, South Australia 5005, Australia
2-glycoprotein I (2GPI) have been proposed to
be clinically relevant because of their strong association with
thrombosis, miscarriage, and thrombocytopenia. By using a homologous
recombination approach, 2GPI-null mice were generated to begin to
understand the physiologic and pathologic role of this prominent plasma
protein in mammals. When 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
2GPI plays a beneficial role in implantation and/or fetal
development in at least some mouse strains. Although those 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, 2GPI also appears to play an important role in
thrombin-mediated coagulation.
*
This work was supported by the National Health and Medical
Research Council (Australia) and the Clive and Vera Ramaciotti Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Immunology, Allergy, and Infectious Disease, St. George Hospital, South St., Kogarah, 2217 New South Wales, Australia. Tel.: 61-2-93502955; Fax: 61-2-93503981; E-mail: s.krilis@unsw.edu.au.
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