PROJECT 6

该提案的一个重要目标是将遗传和生理系统的综合计算建模与定义菌株的实验研究联系起来。在整个项目1-4中，提出了使用最近开发的模型和产生几种新的动物模型。我们将用我们 在大鼠育种和高通量基因分型、大鼠生殖系转基因、基因敲除以及新开发的基因敲入方法方面的专业知识，因为各种项目要求以及新的预测和可检验的假设出现。模型的选择将基于几个标准。首先，也是最重要的，菌株是否可能提供表型信息，这些表型信息可以通过 模拟工具集？第二，基因的破坏是否可能导致一个可行的动物模型？我们将确定是否已成功产生小鼠KO模型。第三，菌株是否可能成为研究界的一个有价值的模型？在项目5中，经验证的模拟工具集将被组合以了解集成系统功能，不同的模型菌株也将通过育种进行组合，以测试集成工具集的模拟。

An important goal of this proposal is to link the integrated computational modeling of genetic and physiological systems to experimental studies in defined strains. Throughout Projects 1-4, the use of already recently developed models and the generation of several new animal models are proposed. We will use our expertise in rat breeding and high throughput genotyping, rat germline transgenesis, gene knockout, as well as newly developed approaches for gene knockin, as the various projects dictate and as new predictions and testable hypotheses emerge. The selection of the models will be based on several criteria. First and most importantly, is the strain likely to give phenotype information that could be modeled or predicted by the simulation toolsets? Second, is disruption of the gene likely to lead to a viable animal model? We will determine whether a mouse KO model has been successfully produced. Thirdly, is the strain likely to be a valuable model to the research community? In Project 5, the validated simulation tool sets will be combined to understand integrated systems function and different model strains will be likewise combined through breeding to test simulations of the integrated toolsets.