FRAGILE ANIMAL MODELS OF HUMAN DISEASE

该计划提出了在动物细胞水平上进行免疫学研究 对普通的非病原体异常敏感，因为 研究的性质。五项互动调查分别侧重于 免疫学和需要特殊细菌遏制技术， 将由核心支助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 为分析发病机制和评价 介入治疗中枢神经系统脊髓灰质炎。计划2 利用白细胞介素-2（IL-2）缺陷小鼠来解决 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将利用人类和犬类之间的相似性 淋巴系统和文件的效用，X连锁严重 联合免疫缺陷（XSCID）犬作为研究人类的模型 淋巴细胞生成和免疫功能。项目4将探索新的方法 延长重组腺病毒介导的基因表达， 重组腺病毒在非人细胞中重介导的能力 灵长类动物的肝脏根据小鼠中类似研究的结果， 将探索短暂免疫抑制或诱导的可行性 免疫无反应性作为改善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 描述了糖蛋白A在特异性相互作用中的作用， 卡氏肺孢子虫与宿主上皮细胞的关系， 这种微生物介导肺孢子虫引起的严重肺损伤 Carnii肺炎是患者发病和死亡的主要原因 获得性免疫缺陷综合症（艾滋病）以及常见的 危及生命的机会性感染 患者高级研究员将提供宝贵的研究指导 实验室动物医学博士后兽医 训练我们预计，在该计划的拟议期间， 研究将提升到重大研究举措的层面。我们预计 在本计划的拟议期间，这些研究将 提升到重大研究举措的层面。这五个项目是 在动物资源管理核心股的支持下， gnotobiotic技术支持，无菌隔离器和高效率 颗粒空气（HEPA）过滤外壳，疾病诊断监测 各种研究服务。与数据的交互产生了 gnotobiology政策，并导致建立一个中心， 支持免疫功能低下动物研究的昆虫生物学。

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.