Characterisation of an in-vivo thrombosis animal model of the antiphospholipid syndrome using Beta 2-GPI KO mice

使用 Beta 2-GPI KO 小鼠表征抗磷脂综合征体内血栓形成动物模型

• 批准号: nhmrc : 209500
• 负责人: Prof Steven Krilis
• 金额: $ 31.16万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/characterisation-an-in-ko-mice/76040
• 关键词: Characterisation; vivo; thrombosis; animal; model

The antiphospholipid syndrome is an autoimmune condition characterised by the presence of thrombosis and recurrent miscarriage. The disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2- Glycoprotein I. This protein has been thought to be important in controlling the clotting system in humans and other mammals. However, the experiments that have been designed to look at the function of this protein have looked at its function in the test tube. The exact role of Beta 2-GPI in the body, has not been determined. A way of looking at the function of this protein in the body would be if you eliminated the protein from an animal such as a mouse. By sophisticated molecular biology techniques 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 are an ideal animal model to examine the function of Beta 2-GPI. Experiments outlined in this proposal will examine the role of Beta 2-GPI in clotting, atherosclerosis and the effect of production of antibodies to Beta 2-GPI in these animals. In addition, since current treatment of patients that have these antibodies consists of long term, sometimes lifelong, treatment with drugs that thin the blood which have potential side effects, we are investigating a novel treatment approach which is directed at eliminating the antibodies that bind Beta 2-GPI. If one could eliminate the antibody production to Beta 2-GPI by these patients there would not be a need for lifelong treatment with drugs such as heparin which thins the blood and there would thus be a reduction in the problems with these medications. To do this we have obtained a specialised chemically modified portion of Beta 2-GPI that has already been shown to work in preliminary experiments.

抗磷脂综合征是一种自身免疫性疾病，其特征是血栓形成和复发性流产。这种疾病的特征是循环抗体结合血液中称为β 2-糖蛋白I的蛋白质。这种蛋白质被认为在控制人类和其他哺乳动物的凝血系统中很重要。然而，旨在观察这种蛋白质功能的实验已经在试管中观察了它的功能。β 2-GPI在体内的确切作用尚未确定。一种观察这种蛋白质在体内功能的方法是，如果你从动物（如小鼠）中消除这种蛋白质。通过复杂的分子生物学技术，我们已经能够消除小鼠中的β 2-GPI基因，从而获得不产生任何β 2-GPI蛋白的小鼠。这些小鼠被称为Beta 2-GPI敲除小鼠，是检查Beta 2-GPI功能的理想动物模型。本提案中概述的实验将检查β 2-GPI在凝血、动脉粥样硬化中的作用以及这些动物中β 2-GPI抗体产生的影响。此外，由于目前对具有这些抗体的患者的治疗包括使用具有潜在副作用的稀释血液的药物进行长期，有时是终身治疗，因此我们正在研究一种新的治疗方法，该方法旨在消除结合β 2-GPI的抗体。如果可以消除这些患者产生的β 2-GPI抗体，就不需要终身使用肝素等稀释血液的药物进行治疗，从而减少这些药物的问题。为了做到这一点，我们已经获得了β 2-GPI的一个专门的化学修饰部分，该部分已经在初步实验中显示出工作。