Animal Core

描述(由申请人提供)： 在本项目中，大鼠和小鼠被选为体内和许多体外研究的中心动物模型。大鼠和小鼠特别适合于这些研究，因为这个项目的参与者已经积累了大量关于心脏移植和动脉粥样硬化的数据库，这些数据库可以在文献中找到。 动物核心已经作为体内AGA模型的公共资源运行了五年。拥有动物核心的主要好处是通过共享来自对照和实验性心脏移植的材料来优化动物的使用，这些材料是以统一的技术专业知识进行的。这促进了不同项目使用的所有模型中发生的血管病变的比较。在关键动物模型开发过程中，动物核心在促进协作使用方面的作用。这方面的一个例子是使用各种基因敲除小鼠。在确定了iNOS在B10排斥反应中的重要性后，对有iNOS基因敲除的C57BL/6受者的同种异体心脏移植，这种菌株组合被扩展为与eNOS、von Willebrand因子和P-选择素基因敲除(由Lowenstein博士)以及颗粒酶B(由Rosen博士敲除)一起使用。采用统一的免疫抑制方法(用抗CD4的单抗治疗)以防止急性排斥反应。因此，可以使用共同的对照，并可以在试验组之间对共同感兴趣的终点进行比较，如细胞浸润、内皮损伤和von Willebrand因子的释放。所有拟议的项目将继续使用同种异体心脏移植的动物模型。三个项目将使用老鼠和大鼠，两个项目将主要使用老鼠或大鼠。

DESCRIPTION (provided by applicant): The rat and mouse have been chosen as the central animal models for in vivo and many in vitro studies in this program project. Rats and mice are uniquely suited for these investigations because of the large data base on cardiac transplants and atherosclerosis that the participants in this program project have already accumulated and that are available in the literature. The Animal Core has been functioning for five years as a common resource for in vivo models of AGA. The major benefit of having an Animal Core is the optimized use of animals by sharing material from control and experimental cardiac transplants that are performed with a uniform technical expertise. This has promoted the comparison of vascular lesions that develop in all of the models used by different projects. The role of the animal core in facilitating collaborative use of critical animal models as they are developed. One example of this is the use of various knock out mice. After the importance of iNOS was established in the rejection of B 10.A cardiac allografts to C57BL/6 recipients with iNOS knock outs, this strain combination was expanded for use with eNOS, von Willebrand factor and P-selectin knock outs by Dr. Lowenstein, and Granzyme B knock outs by Dr. Rosen. A uniform method of immunosuppression was adopted (treatment with monoclonal antibodies to CD4) to prevent acute rejection. As a result common controls could be used and comparisons among experimental groups could be made for end points of common interest, such as cellular infiltrates, endothelial injury and release of von Willebrand factor. Animal models of cardiac allografts will continue to be used in all of the proposed projects. Three projects will make use of mice and rats and two projects will use primarily just mice or rats.