Antiphospholipid Antibodies, Beta 2-Glycoprotein I and control of coagulation.

抗磷脂抗体、Beta 2-糖蛋白 I 和凝血控制。

• 批准号: nhmrc : 350846
• 负责人: Prof Steven Krilis
• 金额: $ 31.41万
• 依托单位: The University of New South Wales
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/antiphospholipid-antibodies-beta-control-coagulation/100226
• 关键词: Antiphospholipid; Antibodies; Beta; Glycoprotein; control

Antiphospholipid antibodies are associated with an autoimmune condition characterised by the presence of clots and recurrent miscarriages. Although the name implies that the antibodies bind phospholipid the disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2-Glycoprotein I. The exact role of Beta 2-GPI in the body has not been determined, although there are numerous studies looking at this protein. This protein has been thought to be important in controlling the clotting system in humans and other mammals. The evidence for this has been contradictory, however, we have recently made a major new finding on the function of this protein on the clotting system. We will be using sophisticated molecular biology techniques to further characterise the role that Beta 2-GPI has in controlling clotting factors in the body. We have been able to eliminate the gene for Beta 2-GPI in mice thus deriving mice that do not produce any Beta 2-GPI protein. These mice are called Beta 2-GPI knockout mice and will be an ideal animal model to examine the function of Beta 2-GPI and its new role in controlling the clotting cascade by targetting a specific part of this pathway. In addition, these findings may be able to provide new information on how Beta 2-GPI controls clotting factors and the effect of antiphospholipid antibodies on this system, which may lead to new treatments for antiphospholipid antibodies and more generally clotting disorders.

抗磷脂抗体与以血块和复发性流产为特征的自身免疫性疾病有关。虽然这个名字暗示了抗体与磷脂结合，但这种疾病的特点是循环抗体与血液中称为β 2-糖蛋白i的蛋白质结合。β 2-GPI在体内的确切作用尚未确定，尽管有许多研究关注这种蛋白质。这种蛋白质被认为对控制人类和其他哺乳动物的凝血系统很重要。这方面的证据一直是矛盾的，然而，我们最近在这种蛋白质对凝血系统的功能方面有了重大的新发现。我们将使用复杂的分子生物学技术来进一步表征β 2-GPI在控制体内凝血因子中的作用。我们已经能够消除小鼠体内的β 2-GPI基因，从而得到不产生任何β 2-GPI蛋白的小鼠。这些小鼠被称为β 2-GPI敲除小鼠，它们将成为研究β 2-GPI功能及其通过靶向该途径的特定部分在控制凝血级联中的新作用的理想动物模型。此外，这些发现可能能够为β 2-GPI如何控制凝血因子以及抗磷脂抗体对该系统的影响提供新的信息，这可能会导致抗磷脂抗体和更普遍的凝血障碍的新治疗方法。