Core C - Proteostasis Animal Models Core

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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.