Core 2 - Animal Models of Inflammatory Disease Core

炎症性疾病动物模型核心的首要任务是支持辛辛那提儿童医院研究社区的研究人员使用风湿性疾病、自身免疫性疾病和炎症过程的实验动物环境。在此过程中，核心将促进对关节炎和自身炎症疾病的理解和治疗。动物模型，特别是涉及小鼠系统的动物模型，已经成为关节炎和自身免疫研究的有力工具，因为任何被确定为候选“疾病修饰因子”的基因都可以通过“基因靶向”或标准转基因技术在小鼠中轻松操纵。动物模型提供了一种体内实验系统，可以适应研究者强加的遗传改变（例如，功能丧失或功能获得），动物模型提供了独特的机会（在人类受试者中无法获得）来测试专注于确定驱动自身炎症性疾病的基本机制的假设。动物模型提供了收集整个组织（即整个关节）的能力，用于详细分析生化、免疫、病理和基因表达特性，以及对疾病进展进行全面的时间分析。这些实验系统通常为一些最强大的治疗策略（例如，抗细胞因子疗法，如TNF阻滞剂）提供了早期的原理证明，这一事实突出了动物模型的效用。最后，许多关节炎和其他自身炎症性疾病的动物模型具有不同的病因（例如，适应性免疫驱动与细胞因子驱动），因此提供了各种不同的框架来研究这些复杂的疾病过程。炎症性疾病动物模型核心的具体目标是(i)为对自身炎症性疾病（即关节炎、神经炎症性疾病和皮肌炎）动物模型感兴趣的研究人员提供技术专长和起始试剂，以及（ii）为转基因和基因靶向小鼠的产生和表征提供物质援助，这些小鼠将对自身炎症性疾病的发生和进展具有指导意义。该核心是辛辛那提风湿病核心中心研究基地正在进行的基础和临床研究（如免疫学、信息学和基因发现）的完美补充。

The over-arching mission of the Animal Models of inflammatory Disease Core is to support investigators of the Cincinnati Children's Hospital Research Community in the use of experimental animal settings of rheumatic diseases, autoimmune diseases, and inflammatory processes. In so doing, the Core will promote advances in the understanding and treatment of arthritic and auto-inflammatory diseases. Animal models, particularly those involving murine systems, have emerged as powerful tools in arthritis and autoimmune research due to the fact that any gene identified as a candidate "disease modifier" can be easily manipulated in mice through either "gene-targeting" or standard transgenic technologies. In providing an in vivo experimental system amenable to investigator-imposed genetic alterations (e.g., loss-of-function or gain-of function), animal models offer the unique opportunity (not available in human subjects) to test hypotheses focused on identifying the fundamental mechanisms that drive auto-inflammatory disease. Animal models offer the ability of collecting entire tissues (i.e., whole joints) for detailed analyses of biochemical, immunological, pathological and gene expression properties, and as well as performing comprehensive temporal analyses of disease progression. The utility of animal models has been highlighted by the fact that these experimental systems have often provided the early proof-of-principle for some of the most powerful therapeutic strategies (e.g., anti-cytokine therapies such as TNF blockers). Finally, many animal models of arthritis and other auto-inflammatory diseases are available with distinct etiologies (e.g., adaptive immune driven vs. cytokine driven), and thus provide a variety of distinct frameworks to study these complex disease processes. The Specific Aims of the Animal Models of Inflammatory Diseases Core are to (i) provide technical expertise and starter reagents to investigators interested in animal models of auto-inflammatory disease (i.e., arthritis, neuroinflammatory disease, and dermatomyositis), and (ii) provide material assistance in the generation and characterization of both transgenic and gene-targeted mice that will be instructive with regard to the development and progression of auto-inflammatory disease. This core serves as the perfect complement to ongoing basic and clinical studies (e.g., immunology, informatics, and gene discovery) of the Cincinnati Rheumatic Diseases Core Center Research Base.