National Gnotobiotic Rodent Resource Center

描述（由申请人提供）：环境因素改变许多慢性疾病的遗传易感性。共生微生物群深刻影响许多器官的生理反应，并在炎症、肿瘤和可能的退行性疾病中发挥重要作用。NGRRC为地方、区域、国家和国际多学科研究人员提供了一个资源，以探索共生菌从根本上影响正常宿主的正常生理过程和遗传易感宿主的致病性炎症和肿瘤反应的假设。本单元为基础广泛的研究人员提供了一个资源，以检查不同遗传背景的无菌（无菌）、已知生物（已知生命）和特定病原体的啮齿动物的生理和病理生理差异，并定义细菌基因的生理和病理生理相关性。微生物群可以通过使用等基因野生型或基因工程菌株，用单一或多种共生或致病细菌或真菌定植无菌啮齿动物来精确控制。具体目标：1；向美国国立卫生研究院资助的研究人员提供无菌或选择性定植的野生型和突变型小鼠和大鼠或其组织和细胞。2. 开发创新技术，有效地获得新的小鼠和大鼠菌株的无菌繁殖菌落，用于要求研究人员和污染细菌的分子检测和鉴定。3. 支持具有新颖假设的研究人员的试点研究，为NIH拨款申请提供初步数据。我们为美国国立卫生研究院（nih）资助的大量不同研究人员提供了一个独特而重要的资源，以研究共生细菌定植的生理和病理生理后果，特别强调基因/环境相互作用在改变生理和疾病表型的转基因小鼠（转基因、基因敲除或自发突变）中。在我们最初的4年资助中，NGRRC为35个机构的61名研究人员提供了4621只非生物小鼠和大鼠。由32名研究人员资助的39项资助和11项提交的资助依赖于NGRRC的非生物动物。我们的设施的独特之处在于1)与UNC突变小鼠区域资源中心（MMRRC）的互动，2)申请团队的经验，3)胚胎移植和冷冻保存的创新，4)外部研究人员现场组织收集的选择，5)训练有素的技术人员为申请研究人员收集组织或分离细胞。

DESCRIPTION (provided by applicant): Environmental factors modify genetic susceptibility to many chronic diseases. Commensal microbiota profoundly influence physiologic responses in a number of organs and heavily contribute to inflammatory, neoplastic and possibly degenerative diseases. The NGRRC provides a resource for local, regional, national and international multidisciplinary investigators to explore the hypothesis that commensal bacteria fundamentally Influence normal physiologic processes in normal hosts and pathogenic inflammatory and neoplastic responses in genetically susceptible hosts. This unit provides a resource for broadly based investigators to examine physiologic and pathophysiologic differences in germ-free (sterile) vs. gnotobiotic (known life) vs. specific pathogen-free rodents of different genetic backgrounds, and to define the physiologic and pathophysiologic relevance of bacterial genes. The microbiota can be precisely manipulated by colonizing germ-free rodents with single or multiple commensal or pathogenic bacterial or fungal species, using isogenic wild type or genetically engineered bacterial strains. Specific aims: 1. Provide germ-free or selectively colonized wild type and mutant mice and rats or their tissues and cells to NIH-funded investigators. 2. Develop innovative techniques to efficiently derive germ-free breeding colonies of new strains of mice and rats for requesting investigators and for the molecular detection and identification of contaminating bacteria. 3. Support pilot studies for investigators with novel hypotheses to generate preliminary data for NIH grant applications. We provide a unique and essential resource for a large, diverse group of NIH-funded investigators to study the physiologic and pathophysiologic consequences of colonization by commensal bacteria, with particular emphasis on gene/environmental interactions in genetically altered mice (transgenic, knockout or spontaneously mutated) with altered physiology and disease phenotypes. In our initial 4 years of funding, the NGRRC has provided 4621 gnotobiotic mice and rats to 61 investigators in 35 institutions. 39 funded and 11 submitted grants by 32 investigators depend on gnotobiotic animals from the NGRRC. Unique features of our facility are 1) interaction with the UNC Mutant Mouse Regional Resource Center (MMRRC), 2) the experience of the applicant team, 3) innovation in embryo transfer and cryopreservation, 4) The option for onsite tissue collection by external investigators, 5) highly trained technical staff to collect tissues or isolate cells for requesting investigators. PUBLIC HEALTH RELEVANCE (provided by applicant): The NGRRC provides a local, regional, national and international resource for NIH-funded investigators to explore the role of commensal bacteria on normal physiologic and pathophysiologic processes in wild type and genetically engineered rodents and trains investigators and staff in other facilities in gnotobiotic technology. The research component of this application explores novel ways of deriving gnotobiotic mice and using molecular techniques to detect and identify contaminating organisms. In addition, it permits investigators to obtain preliminary data to submit competitive grant applications. In the past funding cycle these preliminary data and access to our facility resulted in 6 new funded grants.