Product Testing Animal Core

产品测试动物核心（PTAC） 项目摘要 产品测试动物中心（PTAC）将提供：1）高质量的无菌小鼠，2）体内评价 辐射抑制剂，3）辐射效应的无菌模型，以及4）关于动物研究问题的支持， 规定PTAC的平台是特殊的，因为它管理，繁殖和维护自己的鼠标 殖民地30多年来，该动物园一直保持着极高质量的非细菌设施 那里的动物有明确的微生物群。在小鼠中进行的实验是最高质量的， 如果要获得有意义的结果，微生物和遗传学的观点是必不可少的。此外，建立 一个绝对无菌，或纯，小鼠菌落内的gnotobiotic设施已启动， PTAC计划对其进行扩展，以满足CMCR项目的需求。微生物参与了 维持宿主生理和由于细菌移位引起的急性辐射综合征（ARS）， 脓毒症是由免疫抑制引起的，这一点已经讨论了很久。无菌动物将促进 CMRC使命旨在确定优化正常组织辐射抗性的特定试剂或方案 通过消除微生物在ARS中的作用和急性辐射暴露的延迟效应。该设施目前 为大约113名在辐射、DNA修复、免疫学和癌症领域工作的研究人员提供服务。 它培育了140多个品系，每年59，000只正常，免疫缺陷和转基因小鼠，所有这些小鼠都是 CMCR调查人员可访问。作为新药开发管道的一部分，PTAC利用这种 内部动物模型，将表征药代动力学并检查放射性疗效 从产品开发核心（PDC）筛选的化合物。吸收、分布、代谢和 将与PDC一起对潜在候选药物进行ADME评估。 随后，PTAC将使用充分表征的临床前动物模型来测试化合物， 减轻体内辐射诱导损伤的能力。此外，由于ARS是一种多器官现象， 关注单个系统不一定反映潜在缓解措施在 有机体因此，PTAC将利用其在电离辐射影响方面的丰富经验， 分子水平上的多种正常组织（骨髓、肠、肺、皮肤、肾、脑和脊髓）， 细胞和整个组织水平。最后，像加州大学洛杉矶分校的所有设施一样，与PTAC相关的殖民地完全是AAALAC- 认证，是在加州大学洛杉矶分校的鼠标机构皇冠上的宝石，具有悠久的历史， 与IACUC合作。PTAC将在促进动物研究方面发挥重要作用， CMRC，整合项目，标准化来自个别研究的信息，并使 为即将到来的未来临床研究开发可行的新药，以满足CMCR使命。

PRODUCT TESTING ANIMAL CORE (PTAC) PROJECT SUMMARY The Product Testing Animal Core (PTAC) will provide: 1) high-quality gnotobiotic mice, 2) in vivo evaluation of radiomitigators, 3) axenic models of radiation effects, and 4) support regarding animal research issues and regulations. The PTAC's platforms are exceptional because it manages, breeds, and maintains its own mouse colony. For over 30 years, the vivarium has been maintained as an extremely high-quality gnotobiotic facility where animals have a defined microbiota. Performing experiments in mice that are of the highest quality from microbial and genetic standpoints is essential if meaningful results are to be obtained. Further, establishment of an absolutely germfree, or axenic, mouse colony within the gnotobiotic facility has been initiated and the PTAC plans to expand it to accommodate the needs of the CMCR Projects. The involvement of microbes in the maintenance of host physiology and in acute radiation syndrome (ARS) due to bacterial translocation and sepsis, aided and abetted by immunosuppression, has long been discussed. Germfree animals will facilitate the CMRC mission aimed at identifying specific agents or regimens that optimize normal tissue radioresistance by eliminating a role for microbes in ARS and delayed effects of acute radiation exposure. The facility currently serves approximately 113 investigators working in the fields of radiation, DNA repair, immunology, and cancer. It breeds over 140 strains, 59,000 per year, of normal, immune deficient, and transgenic mice all of which are accessible to CMCR investigators. As part of the pipeline for new drug development, the PTAC, utilizing such in-house animal models, will characterize the pharmacokinetics and examine the radiomitigative efficacy of compounds screened from the Product Development Core (PDC). Absorption, distribution, metabolism, and excretion (ADME) assessments will be carried out on potential drug candidates in conjunction with the PDC. Subsequently, the PTAC will use well-characterized preclinical animal models to test compounds for their ability to mitigate radiation-induced damage in vivo. Furthermore, because ARS is a multi-organ phenomenon, focus on single systems will not necessarily reflect the total effect of a potential mitigator in the context of the organism. Accordingly, the PTAC will exploit its extensive experience with the effects of ionizing radiation on multiple normal tissues (bone marrow, intestine, lung, skin, kidney, brain, and spinal cord) at the molecular, cellular, and whole tissue level. Finally, like all facilities at UCLA, the PTAC-associated colony is fully AAALAC- accredited and is the jewel in the crown of the mouse establishments at UCLA with a long history of cooperation with the IACUC. The PTAC will perform a vital function in facilitating animal research within the CMRC, integrating the Projects, standardizing information derived from individual studies, and enabling development of viable new drugs for imminent future clinical investigation to meet the CMCR mission.