CORE ABSTRACT Animal models in general remain the mainstay of sepsis and trauma research, and the mouse remains the model of choice for mechanistic and interventional studies. Although recent evocative studies by our own group have questioned the value of murine models in inflammation research in general, we have successfully developed and validated a murine model of chronic critical illness (CCI) in response to sepsis that recapitulates much of the underlying processes seen in human persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Animal Studies Core has the overarching goal of providing the Program with transgenic animals and models that are an adjunct to the observational clinical studies, and are meant to test specific hypotheses, and to mechanistically dissect individual contributions to the host response. Therefore, the three specific aims are as follows: 1. To establish a central core resource for the conduct of the studies using the murine model of polymicrobial sepsis, produced by cecal ligation and puncture (CLP). a. to continue development of the CLP model to more closely approximate the human setting of sepsis or severe sepsis. 2. To maintain breeding colonies of wild-type (C57BL/6 (B6)), C57BL/6CD45.1 (B6.SLJ) and transgenic (b-common receptor (b-CR)) mice. 3. To work with the Administration Core to assist individual investigators with compliance regarding the regulatory responsibilities and management of mice used in the individual projects. The Animal Studies Core is an essential component of the University of Florida Sepsis and Critical Illness Research Center. By centralizing animal protocols and management into a single Core, the Program achieves: (1) efficiency in resource utilization, (2) assurance of standardized procedures of animal models with reproducible outcomes, (3) centralized animal purchasing and maintenance, and (4) consolidated communication with the IACUC and Institutional Animal Care Services to maintain an appropriate oversight for the humane use of living animals in USDA Category E research. Reproducible, well described and published models of sepsis and chronic critical illness are the requisite tools to complement the clinical investigations. The Animal Studies Core will provide these services and tools.

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