Product Testing Animal Core

产品测试动物核心(PTAC) 项目总结 产品测试动物核心(PTAC)将提供：1)高质量的灵芝小鼠，2)体内评估 放射增强剂，3)辐射效应的无菌模型，以及4)关于动物研究问题和 规章制度。PTAC的平台是例外的，因为它管理、繁育和维护自己的老鼠 殖民地。30多年来，间隔室一直是一个极高质量的灵知生菌设施。 那里的动物有一个明确的微生物区系。在小鼠身上进行实验，这些小鼠是从 如果要获得有意义的结果，微生物和遗传观点是必不可少的。此外，编制 已经开始在灵知生菌设施内建立一个绝对无菌或无菌的小鼠群体，并且 PTAC计划扩大它，以适应CMCR项目的需要。微生物在生物多样性中的作用 宿主生理的维持和细菌易位引起的急性辐射综合征(ARS)和 脓毒症，免疫抑制的辅助和教唆，长期以来一直被讨论。无菌动物将促进 CMRC的任务旨在确定特定的药物或方案，以优化正常组织的辐射抗性 通过消除微生物在急性呼吸窘迫综合征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。 它每年培育超过140个品系的正常、免疫缺陷和转基因小鼠，所有这些小鼠都是 CMCR调查人员可以访问。作为新药开发流水线的一部分，PTAC利用 内部动物模型，将表征药物动力学并检查其放射增敏效果 从产品开发核心(PDC)筛选出的化合物。吸收、分布、新陈代谢和 将与PDC一起对潜在的候选药物进行排泄(ADME)评估。 随后，PTAC将使用特征良好的临床前动物模型来测试化合物的 在体内减轻辐射损伤的能力。此外，由于ARS是一种多器官现象， 将重点放在单个系统上不一定反映潜在缓释剂在 有机体。因此，技术咨询委员会将利用其在电离辐射影响方面的丰富经验。 多个正常组织(骨髓、肠、肺、皮肤、肾脏、脑和脊髓)在分子， 细胞水平和整个组织水平。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- 是加州大学洛杉矶分校老鼠机构皇冠上的明珠，拥有悠久的 与IACUC的合作。PTAC将在促进动物研究方面发挥至关重要的作用 CMRC，整合项目，标准化来自个别研究的信息，并使 为即将到来的临床研究开发可行的新药，以满足CMCR的任务。

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.