Product Testing Animal Core

产品测试动物核心

• 批准号: 9123521
• 负责人: Keisuke S. Iwamoto
• 金额: $ 67.06万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9123521
• 关键词: Acute; Animal Experimentation; Animal Model; Animal Testing; Animals; Bacterial Translocation; Bone Marrow; Brain; Breeding; Cancer Immunology Science; DNA Repair; Dental crowns; Development; Drug Kinetics; Evaluation; Excretory function; Future; Gnotobiotic; Housing; IACUC; Immune; Immunosuppression; Individual; Intestines; Ionizing radiation; Kidney; Lung; Maintenance; Medical center; Metabolism; Microbe; Microbial Genetics; Mission; Modeling; Molecular; Mus; Normal tissue morphology; Organ; Organism; Physiology; Radiation; Radiation Toxicity; Radiation induced damage; Radioresistance; Recording of previous events; Regimen; Regulation; Research Personnel; Role; Sepsis; Skin; Spinal Cord; System; Testing; Tissues; Transgenic Mice; Work; absorption; animal facility; clinical investigation; cost; drug candidate; drug development; experience; in vivo; meetings; microbiota; novel therapeutics; pre-clinical; product development; radiation effect; research study

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.

产品测试动物核心 (PTAC) 项目概要 产品测试动物核心 (PTAC) 将提供：1) 高质量的无菌小鼠，2) 体内评估 辐射缓解剂，3）辐射效应的纯模型，以及 4）有关动物研究问题和 法规。 PTAC 的平台非常出色，因为它管理、繁殖和维护自己的小鼠 殖民地。 30 多年来，动物园一直保持着极高品质的知生设施的地位 动物有明确的微生物群。在最高质量的小鼠身上进行实验 如果要获得有意义的结果，微生物和遗传学的观点至关重要。进一步，设立 在无菌设施内建立绝对无菌或无菌的小鼠群体已经启动，并且 PTAC 计划对其进行扩展以满足 CMCR 项目的需求。微生物的参与 维持宿主生理机能以及由于细菌易位和引起的急性放射综合征（ARS） 长期以来，人们一直在讨论免疫抑制导致的脓毒症。无菌动物将有助于 CMRC 的任务旨在确定优化正常组织放射抗性的特定药物或方案 通过消除微生物在 ARS 中的作用以及急性辐射暴露的延迟效应。该设施目前 为大约 113 名辐射、DNA 修复、免疫学和癌症领域的研究人员提供服务。 它培育 140 多个品系，每年 59,000 只，包括正常小鼠、免疫缺陷小鼠和转基因小鼠，所有这些小鼠都是 CMCR 调查人员可以访问。作为新药开发流程的一部分，PTAC 利用此类 内部动物模型，将表征药代动力学并检查放射缓解功效 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效果 减轻体内辐射引起的损伤的能力。此外，由于 ARS 是一种多器官现象， 关注单一系统不一定能反映潜在缓解措施在环境中的总体影响 生物。因此，PTAC 将利用其在电离辐射对人体影响方面的丰富经验 多种正常组织（骨髓、肠、肺、皮肤、肾、脑和脊髓）的分子水平， 细胞和整个组织水平。最后，像 UCLA 的所有设施一样，PTAC 相关群体完全是 AAALAC- 获得认可，是 UCLA 鼠标机构皇冠上的明珠，拥有悠久的历史 与 IACUC 的合作。 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，并启用 为即将到来的未来临床研究开发可行的新药，以满足 CMCR 的使命。