Expression Profiling in Canine Models of Human Disease

描述(由申请人提供)： 大规模的基因表达测量有可能提供关于疾病适应性和非适应性反应机制的丰富信息。然而，在与人类受试者一起工作时，研究疾病进展过程中在严格控制的条件下基因表达的时间变化的能力受到严重限制。我们已经组建了一组合作的研究人员，他们在人类和动物模型中的许多心脏、肺、肾脏和血管疾病的病理生物学研究方面拥有丰富的经验。最重要的是，所有人都对使用犬类人类疾病模型来研究疾病的自然历史和使用连续组织样本进行治疗干预的效果有着长期的兴趣；因此，有大量的生物材料将作为表达谱实验的目标。为了更好地理解心血管、肺、血管和肾脏疾病的适应性和非适应性反应的分子机制，我们建议在人类疾病的犬模型中描述基因表达的全球变化。该建议的目的是：1.生成和验证用于表达谱分析的犬cDNA阵列；2.为拟议的阵列设施的研究活动提供计算和信息学支持，包括实施和维护支持特定组织和区域的基因表达数据分析的数据库，以及开发支持该建议的科学目标的数据分析算法；3.描述狗的基因表达谱，包括表征正常犬心脏中基因表达的区域差异以及在心血管、肺和肾脏疾病模型建立过程中发生的时空变化。为实现这项建议的目标而产生的数据和试剂将构成一个重要和普遍可用的资源，不仅供我们机构的研究人员使用，而且也可供全世界的研究人员使用。我们将使研究人员可以通过万维网轻松获取犬类特有的序列信息。随着表达谱数据的产生，它将被合并到基于网络的犬类基因表达谱数据库中。

DESCRIPTION (provided by applicant): Large-scale measurement of gene expression has the potential to provide a wealth of information regarding the mechanisms of adaptive and maladaptive responses to disease. However, the ability to study temporal changes in gene expression under carefully controlled conditions during disease progression is severely limited when working with human subjects. We have assembled a group of collaborating investigators who have extensive experience in the study of the pathobiology of a number of diseases of the heart, lungs, kidneys and vasculature in humans and animal models. Most importantly, all share a long-standing interest in the use of canine models of human disease to study the natural history of disease and the effects of therapeutic interventions using serial tissue sampling; as a consequence there is a wealth of biological material that will serve as targets for expression profiling experiments. In an effort to better understand the molecular mechanisms of adaptive and maladaptive responses to cardiovascular, pulmonary, vascular and renal disorders we propose to profile global changes in gene expression in canine models of human disease. The aims of this proposal are: 1. Generate and validate canine cDNA arrays for expression profiling; 2. Provide computational and informatics support for the research activities of the proposed array facility including the implementation and maintenance of databases supporting tissue-specific and regional analyses of gene expression data and the development of algorithms for data analyses that support the scientific aims of the proposal; 3. To profile gene expression in the dog including the characterization of regional variations in gene expression in the normal canine heart and spatiotemporal changes that occur during the development of models of cardiovascular, pulmonary and renal disease. The data and reagents generated in performance of the aims of this proposal will constitute an important and generally available resource to investigators not only at our institution but worldwide. We will make canine-specific sequence information easily accessible to investigators over the World Wide Web. As expression profile data is generated, it will be incorporated into a web-based database of canine gene expression profiles.