A national resource for mouse models of Mesothelioma

间皮瘤的小鼠模型已经使人们对这种疾病有了更深入的了解，并确定了潜在的药物治疗方法，其中一些现已转化为临床试验。在现有的模型中，实验室培养的间皮瘤细胞通过皮下注射的方式移植到动物体内。在不同的实验方案中使用具有不同特性的不同细胞系。这项申请将资助建立一个中心资源来维护和分配这些细胞系。此外，我们描述了一种新的转基因小鼠模型，其中暴露于石棉后腹膜腔内迅速诱导间皮瘤，更准确地重现了肿瘤的自然发展。这些小鼠被改造成在它们的间皮瘤细胞中表达一种猴子病毒的致癌蛋白（SV40大T抗原），因为有证据表明这种病毒在间皮瘤的发展中起作用。该申请还寻求资金，以使用MexTAg小鼠来测试预防或治疗间皮瘤的不同疗法的有效性。这些动物使我们能够在比以前的模型更现实的环境中研究这种疾病。在与其他研究小组研究这种癌症生物学不同方面的平行合作研究中，我们计划分析疾病发展的早期变化，并利用蛋白质组学和基因表达研究寻找早期标记。我们预计，该模型将产生与了解人类疾病更直接相关的信息，并将为临床试验提供必要的实验数据。

Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resource to maintain and distribute these cell lines. In addition, we describe a new transgenic mouse model in which mesotheliomas are rapidly induced in the peritoneal cavity after exposure to asbestos, recreating the natural tumour development much more accurately. These mice have been engineered to express the cancer causing protein of a monkey virus (SV40 large T antigen) in their mesothelial cells because it has been suggested that the virus has a role in the development of mesothelioma. This application also seeks funding to use the MexTAg mice to test the usefulness of different therapies for the prevention or treatment of mesothelioma. These animals give us the ability to investigate the disease in a more realistic environment than previous models. In parallel collaborative studies with other groups investigating different aspects of the biology of this cancer, we plan to analyze the earliest changes in the development of the disease and search for early markers using proteomics and gene expression studies. We anticipate that this model will generate information more directly relevant to understanding the human disease and will provide essential experimental data for clinical trials.