National Gnotobiotic Rodent Resource Center

描述（由申请人提供）：环境因素改变了许多慢性疾病的遗传易感性。共生微生物群深刻地影响许多器官的生理反应，并严重促进炎症，肿瘤和可能的退行性疾病。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，以探索肠道细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。该单位提供了一个资源，广泛的基础研究人员检查生理和病理生理差异无菌（无菌）与gnotobiotic（已知的生活）与特定病原体无啮齿动物不同的遗传背景，并确定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同基因野生型或基因工程改造的细菌菌株，用单一或多种病原性或致病性细菌或真菌物种定殖无菌啮齿动物来精确操纵。具体目标：1.向NIH资助的研究者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，有效地获得新品系小鼠和大鼠的无菌繁殖菌落，以满足研究人员的要求，并用于污染细菌的分子检测和鉴定。3.支持研究人员的试点研究与新的假设，以产生初步数据的NIH拨款申请。我们提供了一个独特的和必不可少的资源，为一个大的，不同的NIH资助的研究人员研究的生理和病理生理学后果的殖民地的细菌，特别强调基因/环境的相互作用，在基因改变的小鼠（转基因，敲除或自发突变）与改变的生理和疾病表型。在我们最初的4年资助中，NGRRC已经为35个机构的61名研究人员提供了4621只知生菌小鼠和大鼠。由32名研究人员资助的39项资助和11项提交的赠款取决于NGRRC的gnotobiotic动物。我们设施的独特之处在于：1）与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）外部研究者现场组织收集的选择，5）训练有素的技术人员为请求研究者收集组织或分离细胞。 公共卫生相关性（由申请人提供）：NGRRC为NIH资助的研究人员提供了一个地方、地区、国家和国际资源，以探索肠道细菌对野生型和基因工程啮齿动物正常生理和病理生理过程的作用，并培训研究人员和其他设施的工作人员了解非细菌生物技术。该应用程序的研究部分探索了获得gnotobiotic小鼠的新方法，并使用分子技术来检测和识别污染生物。此外，它允许调查人员获得初步数据，以提交竞争性赠款申请。在过去的资助周期中，这些初步数据和对我们设施的访问导致了6项新的资助赠款。

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.