NATIONAL GNOTOBIOTIC RODENT RESOURCE CENTER: AIDS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。描述（由申请人提供）：本修订后的申请要求扩大由经验丰富的科学家管理的现有高产啮齿动物生物单位，为美国国立卫生研究院资助的研究人员提供国家资源，以探索遗传/环境相互作用。这些非生物小鼠和大鼠将被用来研究与共生菌群或这个复杂生态系统的单个组成部分定殖正常和基因突变宿主的生理和病理生理后果。常用的野生型小鼠和大鼠株将可用于生理学研究，调查各种组织和免疫细胞的发育、分化和适应，而基因工程小鼠（基因敲除和转基因）和近交小鼠和大鼠易患各种炎症和肿瘤疾病(小肠结肠炎、结肠癌、糖尿病、动脉粥样硬化、牙周病、关节炎、狼疮、牛皮癣、性传播疾病等)将可用于研究疾病的发病机制。这些啮齿动物将在无菌条件下繁殖，并保持无菌繁殖菌落。这些生理过程或疾病的发病率和侵袭性将在无菌、确定菌群（单相关或与一种或多种细菌共定殖）、特定的无病原体或常规条件下进行研究。可以通过几种机制获得用于研究的组织：可以将非生物啮齿动物运送给调查人员进行研究，调查人员可以访问该设施进行尸检，或者设施技术人员可以在现场处理组织和细胞，然后通过隔夜快递邮件将样本运送给请求调查人员。这些研究将精确地确定正常细菌的各种成分对疾病发病机制和生理过程的影响，提出新的治疗靶点，确定保护性生物，并通过开辟新的研究领域为研究者提供新的科学机会。包括通过胚胎移植优化无菌小鼠系的无菌衍生和研究细菌诱导免疫介导的结肠炎的机制的创新研究。申请人在维持和研究无菌和单相关大鼠和小鼠方面具有丰富的经验，已经进行了关键的观察，证明了非致病性共生细菌在慢性免疫介导的肠道炎症中的重要作用，并且在无菌衍生，胚胎移植和啮齿动物冷冻保存方面具有记录在案的专业知识。该单位旨在补充和扩展ncrr资助的UNC突变小鼠区域资源中心，以节省成本并最大限度地提高效率和使用这两个设施。申请人已附上来自至少29个机构的超过75名研究人员的承诺信，这些机构来自全国所有地理区域，其中包括2个校内NIH项目的成员。这些跨学科的使用者或感兴趣的研究者研究各种各样的生理过程和疾病模型，由多个NIH研究所、退伍军人‘’‘’管理局和克罗恩‘’‘’和美国结肠炎基金会资助。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): This revised application requests expansion of an existing, highly productive rodent gnotobiotic unit run by experienced scientists to provide a national resource for NIH-funded investigators to explore genetic/environmental interactions. These gnotobiotic mice and rats will be used to investigate the physiologic and pathophysiologic consequences of colonizing normal and genetically mutated hosts with commensal bacterial flora or with individual components of this complex ecosystem. Commonly used wild-type murine and rat strains will be available for physiologic studies investigating the development, differentiation and adaptation of various tissues and immune cells, while genetically engineered mice (knockout and transgenic) and inbred mice and rats susceptible to various inflammatory and neoplastic diseases (enterocolitis, colon cancer, diabetes, atherosclerosis, periodontal disease, arthritis, lupus, psoriasis, sexually transmitted diseases etc.) will be available to study disease pathogenesis. These rodents will be derived into sterile (germ-free) conditions and germ-free breeding colonies will be maintained. These physiologic processes or the incidence and aggressiveness of disease will be studied under germ-free, defined flora (monoassociated or cocolonized with 1 or more bacterial species), specific pathogen free or conventional conditions. Tissues can be obtained for study by several mechanisms: gnotobiotic rodents can be shipped to investigators for study, investigators can visit the facility to perform necropsies, or facility technicians can process tissues and cells on site, then ship samples to requesting investigators by overnight express mail. These studies will precisely determine the influence of various constituents of normal bacteria on disease pathogenesis and physiologic processes, suggest new therapeutic targets, identify protective organisms, and provide new scientific opportunities for investigators by opening new areas of research. Innovative studies to optimize sterile derivation of germ-free mouse lines by embryo transfer and to investigate mechanisms of bacterial induction of immune mediated colitis are included. The applicants have considerable experience in maintaining and investigating germ-free and monoassociated rats and mice, have made pivotal observations demonstrating the essential role of nonpathogenic commensal bacteria in chronic, immunologically-mediated intestinal inflammation, and have documented expertise in sterile derivation, embryo transfer and cryopreservation of rodents. This unit is designed to complement and extend the NCRR-funded UNC Mutant Mouse Regional Resource Center to conserve costs and to maximize efficiency and use of both facilities. The applicants have attached letters of commitment from over 75 investigators from at least 29 institutions, from all geographic regions of the country and include members of 2 intramural NIH programs. These interdisciplinary users or interested investigators study a wide variety of physiologic processes and disease models and are funded by multiple NIH institutes, the Veteran''''s Administration and the Crohn''''s and Colitis Foundation of America.