Core 2 - Animal Models of Inflammatory Disease Core

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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.