FRAGILE ANIMAL MODELS OF HUMAN DISEASE

该计划建议在动物体内进行细胞水平的免疫学研究 对普通的非致病因素非常敏感，因为 研究的性质。这五项互动式调查各侧重于 免疫学和需要特殊的诺维菌素遏制技术和 将由核心支持提供的疾病监测能力。 项目1使用严重联合免疫缺陷(SCID)小鼠作为模型 用于分析发病机制，并用于评估 中枢神经系统李斯特菌病的介入治疗。项目2 利用白介素2(IL-2)缺陷小鼠研究 类似溃疡性结肠炎的炎症性肠病的发病机制 在人类身上。项目3将利用人类和狗之间的相似性 淋巴系统，并记录X连锁Severe的效用 联合免疫缺陷(XSCID)犬作为研究人类的模型 淋巴生成和免疫功能。项目4将探索新的方法 对重组腺病毒介导的基因表达的延长和 重组腺病毒在非人类体内的重排能力 灵长类肝脏。基于在老鼠身上进行的类似研究的结果，研究 将探索暂时性免疫抑制或诱导的可行性 将免疫无反应性作为提高免疫系统有效性的策略 重组腺病毒作为基因治疗载体。项目3建议 描述糖蛋白A在特定的相互作用中的作用 卡氏肺孢子虫与宿主上皮细胞的相互作用及其机制研究 这种微生物在肺孢子虫所见的严重肺损伤中起中介作用 卡尼氏肺炎，患者发病率和死亡率的主要原因 与获得性免疫缺陷综合症(AIDS)以及常见的 其他免疫受损的危及生命的机会性感染 病人。高级调查人员将提供宝贵的研究指导 给实验动物医学兽医博士后实习医生 训练。我们预计，在本计划的拟议期间，这些 研究将推进到重大研究倡议的层面。我们预计 在这项计划的拟议期间，这些研究将 推进到重大研究创举水平。这五个项目是 由动物资源管理核心股提供支助，特别 灵知生菌技术支持、无菌隔离器和高效 微粒空气(HEPA)过滤外壳，疾病诊断监测 以及各种研究服务。与数据的交互已产生 灵知生物学政策，并正在导致建立一个 支持免疫受损动物研究的灵知生物学。

This program proposed cellular level immunology studies in animals made unusually susceptible to ordinary non-pathogenic agents because of the nature of the research. The five interactive investigations each focus on immunology and require special gnotobiotic containment technology and disease monitoring capabilities which will be provided by core support. Project 1 uses the Severe Combined Immunodeficient (SCID) mouse as a model for the analysis mechanisms of pathogenesis and for the evaluation of intervention therapy for central nervous system listeriosis. Project 2 utilizes interleukin-2 (IL-2) deficient mice to address the mechanisms of pathogenesis of inflammatory bowel disease similar to ulcerative colitis in humans. Project 3 will exploit the similarity between human and canine lymphoietic systems and document the utility of the X-linked severe combined immunodeficiency (XSCID) dog as a model for studying human lymphopoiesis and immune function. Project 4 will explore novel approaches to the prolongation of recombinant adenovirus-mediated gene expression and the ability to readminister recombinant adenovirus in the non-human primate liver. Based on results in analogous studies in the mouse, studies will explore the feasibility of transient immunosuppression or induction of immune un-responsiveness as strategy to improve the usefulness of recombinant adenoviruses as gene therapy vectors. Project 3 proposes to characterize the role of glycoprotein A in the specific interaction of Pneumocystis carinii with host epithelial cells and to study mechanisms in which this organism mediates the severe lung injury seen with Pneumocystis carnii pneumonia, the leading cause of morbidity and mortality in patients with the Acquired Immunodeficiency Syndrome (AIDS) as well as a common life-threatening opportunistic infection in other immunocompromised patients. Senior investigators will provide valuable research mentorship to laboratory animal medicine veterinarians in postdoctoral residency training. We expect that during the proposed period of this program these studies will advance to the level of major research initiatives. We expect that during the proposed period of this program, these studies will advanced to the level of major research initiatives. The five projects are supported by a Core Unit for animal resource management, special gnotobiotic technology support, germ free isolators and high efficiency particulate air (HEPA) filtered enclosures, disease diagnostic monitoring and various research services. Interactions to data have generated gnotobiology policies and are leading to the establishment of a Center for Gnotobiology in support of research with immunocompromised animals.