Transgenic Mice for Sensing Bioweapons

用于感知生物武器的转基因小鼠

• 批准号: 6962753
• 负责人: ERIK SELSING
• 金额: $ 18.06万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6962753
• 关键词: Bacillus anthracis; air sampling /monitoring; anaphylaxis; anthrax toxin; biohazard detection; bioterrorism /chemical warfare; death; genetically modified animals; host organism interaction; immunoglobulin E; laboratory mouse; rapid diagnosis; spores

DESCRIPTION (provided by applicant): Rapid detection of the release of weaponized pathogens is critical for public defense against bioterrorist attacks. Continuous surveillance against surprise releases is difficult, particularly in large or remote areas. We propose to develop mouse strains that are genetically hypersensitive to the presence of bioterrorist pathogens and that would exhibit anaphylactic shock and rapid death when exposed to bioweapon organisms. The overall goal is to produce animals that would have dramatic and rapid physiological responses to pathogens and serve as sentinels for pathogen release. The aims of this proposal are directed toward preliminary studies to explore the feasibility of this approach. Although the approach can easily be directed toward most pathogens, these preliminary studies will use Bacillus anthracis as a model bioterrorist organism. One (1) specific aim is to produce mouse strains that carry antibody heavy and light chain transgenes encoding IgE antibodies specific for the BclA protein that is the immunodominant epitope on the exosporium of B. anthracis. These mice (Ax-IgE mice) are designed to have highly elevated anti-anthrax IgE levels that will cause them to have allergic hypersensitivity to exposure to anthrax spores. The remaining aims are to further genetically modify Ax-IgE mice to increase their sensitivity to anthrax. This will be done by crossing the Ax-IgE mice with mice that are deficient for inhibitory factors that have been shown to downregulate allergic reactions. The short-term R21 support will allow these preliminary studies to show the specificity and sensitivity of these genetically modified mice to exposure to anthrax spores. This will indicate the potential effectiveness of this new approach to pathogen surveillance and provide a basis for a series of future studies to expand and refine this technology.

描述（由申请人提供）：快速检测武器病原体的释放对于针对生物恐怖袭击的公共防御至关重要。对惊喜发行的持续监视很困难，尤其是在大型或偏远地区。我们建议开发对生物恐怖病原体存在遗传性过敏的小鼠菌株，当暴露于生物妇女生物体时，这会表现出过敏性休克和快速死亡。总体目标是生产对病原体具有巨大生理反应的动物，并用作病原体释放的前哨。该提案的目的是针对初步研究，以探讨这种方法的可行性。尽管该方法可以很容易地针对大多数病原体，但这些初步研究将使用炭疽芽孢杆菌作为模型生物恐怖主义生物。一个（1）的特定目的是产生携带抗体重链和轻链转基因的小鼠菌株，该抗体编码对BCLA蛋白具有特异性的IgE抗体，该抗体是炭疽芽孢杆菌外孢子上的免疫优势表位。这些小鼠（Ax-Ige小鼠）设计为具有高度升高的抗疫AIGE水平，这会导致它们对暴露于炭疽孢子的过敏性过敏。其余的目的是进一步改变遗传修饰斧头小鼠，以提高其对炭疽的敏感性。这将通过将轴 - IGE小鼠与缺乏抑制性因子的小鼠穿越斧头小鼠来完成。短期R21支持将使这些初步研究能够显示这些遗传改性小鼠对暴露于炭疽孢子的特异性和敏感性。这将表明这种新的病原体监测方法的潜在有效性，并为一系列未来的研究提供了扩展和完善这项技术的基础。