Effective radiation experiments with mice require adherence to strict standards in pre- and post-irradiation care to minimize stress that might confound radiation responses. Since the Projects depend on shared samples, mouse resources in the current grant submission have been centralized in an Animal Core, rather than trying to replicate expertise and experiments in each of the Projects. Centralized mouse handling has a strong positive impact on the quality of the results from the experiments performed and allows a more streamlined integration of data generated across the three Projects. The Animal Core will be responsible for the following: ? Provision of strain- and age-appropriate animals for the proposed studies. ? Maintenance of the two CMCR mouse housing satellite facilities: VAriable Dose-rate External 137Cs irradiator (VADER) and Columbia IND Neutron Facility (CINF). ? Provision of support during experiments. ? Coordination of distribution between the Projects of control and irradiated Non Human Primate (NHP) blood samples. These blood samples will be provided to us through another unrelated project. ? Blood immunophenotyping. Mice will be either acquired from approved commercial vendors or established and bred by the Core in the case of the INK-ATTAC transgenic mice that will be used in Projects 2 and 3 to investigate the contribution of senescent cells to radiation-induced lung disease. At the Satellite Facilities, the Core will be responsible for daily maintenance and mouse care as well as monitoring pain and distress in accordance with IACUC guidelines. The Core will be responsible for the administration of anesthesia and euthanasia, sample collection and sharing, coding and blinding and, for the NHP study, receiving all the animal biofluids pre- and post- irradiation to distribute between the Projects. The Animal Core will perform immunophenotyping and serial blood count studies to assess correlations between radiation biomarkers and the hematological nadirs. Immunophenotyping will also be performed from the NHP blood samples to assess baseline and cell depletion cell counts.
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