NEW MODEL FOR HUMAN DISEASES

这项研究计划将导致实验室的建立 负鼠作为一种独特而合适的哺乳动物模型 对公众重要的多种人类疾病进行研究 健康。我们建议启动六项互动调查，将 为未来人类易感性的大规模研究奠定基础 疾病(广泛归类为癌症和心血管疾病)和 关于他们的开始，进展和治疗。此外，我们预计 在这项计划的拟议期间，试点研究使用 Monodelphis作为研究人类传染病的模型和 人类胎儿发育将进入重大研究阶段 首创精神。 Monodelphis作为实验哺乳动物模型的使用有助于 检测涉及特定基因的遗传效应和相互作用 影响人类的疾病可能很难识别。结果是 可以得出新的假说，这些假说是可以检验的。 与人类受试者的关系。相反，Monodelphis有大量的 对这些研究产生的假设进行测试的可能性 人类的疾病，但只能在动物模型上进行测试。项目 1将增加发病率，确定进展，并生成 恶性黑色素瘤易感性的遗传分析数据， 斑点叉尾轮虫在哺乳阶段暴露于紫外线 仅辐射一项。项目2将检验这样的假设：血管生成 是紫外线诱导间充质形成的先决条件 肿瘤，使用Monodelphis的角膜基质作为模型系统。 项目3将确定特定化疗的有效性 适用于人类的治疗恶性黑色素瘤和 Monodelphis间充质(角膜)瘤，体外和体内应用 活体系统。项目4将研究饮食和基因的影响。 脂蛋白表型与肝细胞癌的发生发展 Mondelphis模型中的动脉粥样硬化。项目5将确定 血清胆固醇对高胆固醇反应的遗传基础， Monodelphis的饱和脂肪饮食，与长期目标一起， 项目4，确定控制饮食的特定基因 响应性。项目6将建立一个基本的联动图 Monodelphis基因组，并将使用这一图谱来识别 其他项目中感兴趣的特定等位基因和表型。 这六个项目由一个动物资源核心单位提供支持 管理、数据管理和分析、各种研究服务以及 行政管理。

This research program will lead to the establishment of the laboratory opossum (Monodelphis domestica) as a unique and appropriate mammal model for research on a variety of human diseases of importance to public health. We propose to initiate six interactive investigations that will form the basis for future large scale studies on susceptibility to human diseases (broadly classified as cancer and cardiovascular disease) and on their initiation, progression, and treatment. Furthermore, we expect that during the proposed period of this program, pilot studies using Monodelphis as a model for investigating human infectious disease and human fetal development will advance to the level of major research initiatives. The use of Monodelphis as an experimental mammal model facilitates the detection of genetic effects and interactions involved in specific diseases that may be difficult to identify in affect humans. The results of these investigations can lead to new hypotheses that can be tested with human subjects. Conversely, Monodelphis has a great deal of potential for testing hypotheses that arise from research on these diseases in humans, but can be tested only on a animal model. Project 1 will enhance the incidence, determine the progression, and generate data for genetic analysis of susceptibility to malignant melanoma, initiated at the suckling stage in Monodelphis by exposure to ultraviolet radiation alone. Project 2 will test the hypothesis that angiogenesis is a prerequisite for ultraviolet radiation-inducted mesenchymal neoplasia, using the corneal stroma in Monodelphis as a model system. Project 3 will determine the effectiveness of specific chemotherapeutic strategies, applicable to humans, for treatment of malignant melanoma and mesenchymal (corneal) neoplasia of Monodelphis, using in vitro and in vivo systems. Project 4 will examine the effects of diet and genotype on lipoprotein phenotypes and the initiation and progression of atherosclerosis in the Mondelphis model. Project 5 will be determine the genetic basis of serum cholesterol response to a high-cholesterol, saturated fat diet in Monodelphis, with the long-term goal, together with Project 4, of identifying specific genes that control dietary responsiveness. Project 6 will establish a basic linkage map of the Monodelphis genome and will use this map to identify associations between specific alleles and the phenotypes of interest in the other projects. The six Projects are supported by a Core Unit for animal resource management, data management and analysis, various research services, and administration.