Core C: Animal Models

项目总结 核心C(动物使用和发展核心)的总体目标是支持开发和使用 本计划项目资助(PPG)中使用的动物模型。核心C的指导原则是有效的 动物的规划和利用，加工和诊断的标准化，服务的可靠性和 对动物模型进行一致的评估，并成为所有动物成本的成本中心。基本的专业知识 中心内设有实验动物医学、临床和解剖病理学。核心是 在兽医生物科学部办公和协调。Stefan Niewiesk博士，核心总监 自2004年以来一直担任动物核心项目的(联席)主任，并积极与所有项目负责人合作 PPG。他拥有兽医微生物学证书和实验动物医学兽医资格(欧洲)。 托马斯·罗索尔博士(联合调查员)，他获得了美国兽医病理学院的认证，将 为核心提供病理评估。PPG的总体主题是分析感染如何与 HTLV-1诱导CD4T细胞增殖，病毒蛋白和整合位点如何影响和维持 以及肿瘤细胞如何与其微环境相互作用。在急性感染后，HTLV-1 在生物体中持续存在，最终导致寡克隆和最终单克隆性增殖 CD4+T细胞的转化。在整合病毒(项目2；Kvaratskhelia)后，肿瘤的形成是 由病毒蛋白Tax和Hbz(项目1和4；Green和Ratner)推动，其中包括改变 调节蛋白的表达模式。这些白血病细胞扩散到整个生物体，并导致 骨溶解，常常是高钙血症(项目3；Weilbaecher和Rosol)。所有项目都将使用MICE和 人免疫系统(His小鼠)作为Core C建立的成人T细胞白血病模型 使用HTLV-1的分子克隆。

PROJECT SUMMARY The overall goal of Core C (Animal Use and Development Core) is to support the development and use of the animal models utilized within this Program Project Grant (PPG). The guiding principals for Core C are efficient planning and utilization of animals, standardization of processing and diagnoses, reliability of service and consistent evaluation of animal models and being a cost center for all animal costs. 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, Core Director has been (Co-) Director of the Animal Core since 2004 and is an active collaborator with all Project Leaders for the PPG. He is certified in Veterinary Microbiology and as a Laboratory Animal Medicine Veterinarian (European). Dr. Thomas Rosol (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 proteins and integration sites 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 and finally monoclonal proliferation and transformation of CD4+ T cells. After integration of the virus (Project 2; Kvaratskhelia), tumorigenesis is driven by the viral proteins Tax and Hbz (Projects 1 and 4; Green and Ratner), which includes altered patterns of expression of regulatory proteins. These leukemic cells spread throughout the organism and cause osteolysis and often hypercalcemia (Project 3; Weilbaecher and Rosol). All projects will use mice with a human immune system (HIS mice) as a model for adult T cell leukemia which has been established by Core C using a molecular clone of HTLV-1.