PROJECT SUMMARY – CORE 2 The overall goal of Core 2 (Animal Model Core) is to support the development and use of the animal models utilized within this Program Project Grant (PPG). The guiding principles for the animal model core are efficient planning and utilization of animals, standardization of processing and diagnoses, reliability of service and consistent evaluation of animal models. The fundamental expertise provided within the core is laboratory animal medicine and clinical and anatomic pathology. The Core is housed and coordinated in the Department of Veterinary Biosciences. Dr. Stefan Niewiesk, proposed Core Director has been Director of the Animal Core since 2004 and is an active collaborator with all of the principal investigators for the PPG. Dr. Niewiesk is a certified in Veterinary Microbiology and in Laboratory Animal Medicine (European College). Dr. Krista La Perle (Co-Investigator), who is certified by the American College of Veterinary Pathology will provide pathological evaluations for the Core. The overall theme of the PPG is to analyze how infection with HTLV-1 induces proliferation of CD4 T cells, how viral latency and proteins influence and maintain transformation and how the tumor cells interact with their microenvironment. After acute infection, HTLV-1 persists in the organism, eventually leading to oligoclonal transformation and outgrowth of CD4 T cells. After establishment and reactivation of viral latency (Project 3: Ratner), tumorigenesis is driven by the viral protein Hbz (Project 1: Green). These leukemic cells spread throughout the organism and cause osteolysis (Project 2: Weilbaecher). All projects will use rabbit and mouse models for adult T cell leukemia, which have been established and/or utilized by Core 2 using a molecular clone of HTLV-1.