This Core has two primary objectives: (1) to formulate and produce all experimental diets required for animal feeding trials to be conducted within the Center;(2) to produce, through breeding, mice of novel genotypes required for the studies designed to test hypotheses relating to underlying mechanism for the actions of botanicals. Experimental diets will be formulated according to the most recent guidelines such that the quantity and quality of the nutrients provided is both appropriate and consistent throughout the life of the Center. Botanicals and bioactive components will be incorporated into experimental diets in amounts that follow principles of allometric scaling and the concept of hormesis. The goal being to test mice at levels of botanicals that will readily translate into human intake/exposure levels. This core will work closely with the Analytical Chemistry Core to conduct quality control analyses on all diets to assure consistency from batchto- batch. This Center will generate nearly 6,000 mice per year to investigate the bioactivity and possible modes of action for the botanicals under study. The impact of botanicals on prostate cancer development will be explored in TRAMP mice, a well-characterized mouse model for this disease. Initial studies in Projects #2 will use some common strains of mice (e.g., C57BI/6) to investigate the impact of botanicals on ischemia-reperfusion injury and host response to bacterial and viral infection, respectively. The role of key signaling pathways for the actions of botanicals will be investigated by using tissue-specific gene deletion techniques (i.e., Cre-flox expression targeting) in all three projects. The role of Nrf2-dependent gene expression in botanical-mediated changes in cell function and health outcomes will be explored using mice with astrocyte-, phagocyte-, and prostate-specific deletions of Keapl. Additional mice with neuronaland astrocyte-specific deletions of N0X2, INOS, and nNOS will be generated to support testing novel hypothesis for Project #2 as research findings dictate.
The incorporation of botanicals and their bioactive constituents into well-defined experimental diets with low background activity is an ideal approach for conducting pre-clinical experimentation in animal models. The complexities of botanicals in both their chemical composition and their modes of action make conducting animal-based studies an important component of pre-clinical screening.
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