Core C - Proteostasis Animal Models Core

摘要 以前的衰老和转基因动物核心现在的蛋白质稳定和衰老动物模型核心（核心C） 并在PP文本中称为“动物核心”，将继续支持体内实验小鼠的需要， 本项目的四个项目的模型（PP）。 该核心的长期目标是为项目提供广泛的年龄控制动物 具有修饰的自噬功能的模型和设计用于体内评估 自噬活性这些动物一直是并将继续是进行研究所必需的。 在所有四个项目中，将描述自噬中与年龄相关的变化对 细胞生物学、器官和系统功能的不同方面。此外，核心还将提供不同的 所有项目使用的阿尔茨海默病小鼠模型，将提供中枢蛋白毒性模型 描述脑中蛋白质稳态的改变如何影响外周组织中的蛋白质稳态平衡 且反之亦然。 核心的具体目标是：1）产生和维持i。转基因动物 不同组织中的自噬; ii.表达自噬报告基因的小鼠;和iii.蛋白毒性遗传模型 2）维持野生型和基因修饰小鼠的年龄控制菌落; 3） 通过协调牺牲动物， 最大限度地利用它们，并通过整合从不同的动物模型中获得的信息， 调查员; 4）促进在此期间所有项目中纳入的小鼠干预措施的统一性 新时期的研究; 5）收集所有人共享的一些转基因小鼠模型的纵向信息 项目，并整合来自相同动物的每个项目的健康跨度信息。 服务：核心将继续提供协助，维护小鼠群体，协调 基因分型，动物治疗（饮食和药物化合物）的管理和监测， 动物解剖、收集组织样本用于储存或组织病理学分析以及连续获取 一个可搜索的动物数据库。 关键人员：主任，由动物技术员协助。主任监督所有的 核心的活动，批准PP成员的动物使用，建立育种计划， 满足项目需要，并监督数据库中的动物信息输入。技术人员 执行与动物群体维护、基因分型、治疗、组织 收集、行为测试和将信息输入数据库。 相关性：该核心提供的服务对本报告所列项目的所有活动至关重要。 PP了解蛋白质稳态在衰老和疾病中的作用，并开发遗传和化学 干预措施来调节衰老过程，作为预防或延迟阿尔茨海默病发作的一种方式。的 动物的集中和共享优化了成本效率，并确保了信息的整合 来自本研究中使用的所有动物模型的不同系统和器官。

Abstract The former Aging and Transgenic Animal Core now Proteostasis and Aging Animal Models Core (Core C) and referred in the PP text as “Animal Core” will continue to support the need for in vivo experimental mouse models of the four projects of this Program Project (PP). The long-term goals of this Core are to provide the projects with a wide repertoire of age-controlled animal models with modified autophagic function and mouse models designed for the in vivo assessment of autophagy activity. These animals have been and will keep being essential for performing studies contained in all four projects that will characterize the consequences of the age-related changes in autophagy on different aspects of cell biology and organ and system function. Furthermore, the core will also supply different mouse models of Alzheimer’s disease used by all projects, which will provide models of central proteotoxicity to characterize how altered proteostasis in the brain may affect proteostatic equilibrium in peripheral tissues and vice versa. The specific aims of the core are: 1) to generate and maintain i. genetically modified animals with altered autophagy in different tissues; ii. mice expressing autophagy reporters; and iii. genetic models of proteotoxicity in Alzheimer’s disease; 2) to maintain age-controlled colonies of wild-type and genetically modified mice; 3) to serve as a link among the investigators in the Program Project by coordinating the sacrifice of animals to maximize their use and by integrating the information obtained from the different animal models by each investigator; 4) to facilitate uniformity in the mouse interventions incorporated in all the projects during this new period; 5) to collect longitudinal information on some of the transgenic mouse models shared by all projects and integrate the heath-span information from each project in the same animals. Services: The core will continue offering assistance with maintenance of the mouse colonies, coordination of genotyping, administration and monitoring of animal treatments (diets and pharmacological compounds), animal dissection, collection of tissue samples for storage or histopathological analysis and continuous access to a searchable animal data base. Key personnel: the director, who is assisted by the animal technicians. The director supervises all the activities of the Core, approves animal use by the PP members, establishes breeding schemes to accommodate the project needs and oversees animal information input in the database. The technicians perform all of the activities related to the maintenance of the animal colonies, genotyping, treatments, tissue collection, behavioral testing and inputs information into the database. Relevance: The services provided by this core are central to all the activities of the projects included in this PP to understand the role of proteostasis in aging and disease and to develop genetic and chemical interventions to modulate the aging process as a way to prevent or delay Alzheimer’s disease onset. The centralization and sharing of animals optimizes cost efficiency and guarantees integration of information coming from different systems and organs in all animal models used in this study.