The Aging and Transgenic Animal Core (Core C) will continue to support the need for in vivo experimental mouse models of the four projects of this Program Project. The long-term goals of this Core is to provide the projects with a wide repertoire of age-controlled animal models with modified autophagic function in different tissues and to develop new mouse models for the study of autophagy in a whole organisms. 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.
The specific aims of the core are: 1) to generate and maintain genetically modified animals with altered autophagy in different tissues;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 life-span 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;6) to work closely with Core B in the characterization of the novel CMA reporter mouse models. The services offered by the Core include: 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. The key personnel of the Core are the director, who is assisted by the animal technician. 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 technician performs all of the activities related to the maintenance of the animal colonies, genotyping, treatments, tissue collection, behavioral testing and inputs information into the database.
All four Projects require the use of similar mouse models but focus on different tissues. Centralizing the procedures involving animals in the Core: 1) maximizes animal use;2) offers uniformity across the different projects;and 3) allows integration of the information obtained from different systems by the different projects. The interventions performed by the core to modulate autophagy may help set the basis for future anti-aging interventions.
|Valdor, Rut; Mocholi, Enric; Botbol, Yair et al. (2014) Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation. Nat Immunol 15:1046-54|
|Cuervo, Ana Maria; Macian, Fernando (2014) Autophagy and the immune function in aging. Curr Opin Immunol 29:97-104|
|Quintavalle, Cristina; Di Costanzo, Stefania; Zanca, Ciro et al. (2014) Phosphorylation-regulated degradation of the tumor-suppressor form of PED by chaperone-mediated autophagy in lung cancer cells. J Cell Physiol 229:1359-68|
|Morimoto, Richard I; Cuervo, Ana Maria (2014) Proteostasis and the aging proteome in health and disease. J Gerontol A Biol Sci Med Sci 69 Suppl 1:S33-8|
|Bejarano, Eloy; Yuste, Andrea; Patel, Bindi et al. (2014) Connexins modulate autophagosome biogenesis. Nat Cell Biol 16:401-14|
|Schneider, Jaime L; Cuervo, Ana Maria (2014) Autophagy and human disease: emerging themes. Curr Opin Genet Dev 26:16-23|
|Schneider, Jaime L; Cuervo, Ana Maria (2014) Liver autophagy: much more than just taking out the trash. Nat Rev Gastroenterol Hepatol 11:187-200|
|Cuervo, Ana Maria; Wong, Esther (2014) Chaperone-mediated autophagy: roles in disease and aging. Cell Res 24:92-104|
|Balch, William E; Sznajder, Jacob I; Budinger, Scott et al. (2014) Malfolded protein structure and proteostasis in lung diseases. Am J Respir Crit Care Med 189:96-103|
|Schneider, Jaime L; Suh, Yousin; Cuervo, Ana Maria (2014) Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation. Cell Metab 20:417-32|
Showing the most recent 10 out of 60 publications