A national resource for mouse models of Mesothelioma

间皮瘤的小鼠模型使人们对这种疾病有了更好的了解，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，已在实验室培养的间皮瘤细胞通过将细胞注射到皮肤下移植到动物体内。不同性质的细胞系用于不同的实验方案。这项申请将资助建立一个中央资源，以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，在该模型中，暴露于石棉后，间皮瘤在腹膜腔内迅速诱导，更准确地再现了自然肿瘤的发展。这些小鼠被改造成在它们的间皮细胞中表达猴子病毒的致癌蛋白(SV40大T抗原)，因为已经表明该病毒在间皮瘤的发展中起到了作用。这项申请还寻求资金，以使用MexTAg小鼠来测试不同疗法对预防或治疗间皮瘤的有效性。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。在与其他研究这种癌症生物学不同方面的研究小组的平行合作研究中，我们计划分析疾病发展的最早变化，并利用蛋白质组学和基因表达研究寻找早期标志物。我们预计，该模型将产生与理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.