Core C - Proteostasis Animal Models Core

核心 C - 蛋白质稳态动物模型核心

• 批准号: 10602543
• 负责人: Fernando Macian
• 金额: $ 54.26万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602543
• 关键词: Address; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Animal Diseases; Animal Model; Animal Technicians; Animals; Area; Autophagocytosis; Biology of Aging; Brain; Breeding; Cellular biology; Chemicals; Consultations; Cost efficiency; Data; Databases; Diet; Disease; Disease Progression; Dissection; Equilibrium; Future; Genetic; Genetic Models; Genetically Modified Animals; Genotype; Geroscience; Goals; Health; Human Resources; Individual; Intervention; Intranet; Laboratories; Link; Longevity; Maintenance; Modeling; Monitor; Mus; Online Systems; Onset of illness; Organ; Peripheral; Procedures; Process; Regulation; Reporter; Reporting; Research; Research Personnel; Resources; Role; Scheme; Schools; Series; Services; System; Testing; Text; Therapeutic; Tissue Banks; Tissue Sample; Tissues; Transgenic Animals; Transgenic Mice; Veterinarians; Weaning; age related; aged; aging gene; animal care; animal colony; animal data; animal facility; anti aging; behavior test; design; experimental study; functional restoration; healthspan; improved; in vivo; interest; member; model design; mouse model; pharmacologic; prevent; programs; proteostasis; proteotoxicity

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.

抽象的 以前的衰老和转基因动物核心现在是蛋白质稳态和衰老动物模型核心（核心 C） 并在 PP 文本中称为“Animal Core”，将继续支持体内实验小鼠的需求 本计划项目（PP）的四个项目的模型。 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专为体内评估而设计的小鼠模型 自噬活性。这些动物已经并将继续对于进行包含的研究至关重要 在所有四个项目中，这些项目将描述与年龄相关的自噬变化对 细胞生物学以及器官和系统功能的不同方面。此外，该核心还将提供不同的 所有项目均使用阿尔茨海默病小鼠模型，这将提供中枢蛋白毒性模型 描述大脑中蛋白质稳态的改变如何影响周围组织的蛋白质稳态平衡 反之亦然。 核心的具体目标是： 1）生成并维护i。基因改造动物 不同组织中的自噬；二.表达自噬记者的小鼠；和 iii.蛋白质毒性的遗传模型 阿尔茨海默病； 2) 维持野生型和转基因小鼠的年龄控制群体； 3） 通过协调动物的牺牲，作为项目研究人员之间的纽带 最大限度地利用它们，并通过整合每个人从不同动物模型获得的信息 研究者; 4) 促进在此期间所有项目中纳入小鼠干预措施的统一性 新时期； 5）收集所有人共享的一些转基因小鼠模型的纵向信息 项目并将每个项目的健康跨度信息整合到相同的动物中。 服务：核心将继续提供小鼠群体维护、协调等方面的帮助 动物治疗（饮食和药理学化合物）的基因分型、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 到可搜索的动物数据库。 主要人员：主任，动物技术人员协助。导演监督所有 核心活动，批准 PP 成员使用动物，制定育种计划 满足项目需求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、组织相关的所有活动 收集、行为测试并将信息输入数据库。 相关性：该核心提供的服务对于该核心所包含的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 调节衰老过程的干预措施作为预防或延缓阿尔茨海默病发病的一种方法。这 动物的集中和共享优化了成本效率并保证了信息整合 来自本研究中使用的所有动物模型的不同系统和器官。