Animal Core (Core D)

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SUMMARY: ANIMAL CORE (CORE D) Investigations into brain tumor biology and therapy are best carried out in orthotopic animal models that mimic the natural milieu of the tumor. The ability to reach meaningful conclusions from these in vivo studies is greatly enhanced when uniform, readily reproducible animal models are used. The core also provides support for investigators using genetically engineered mouse models (in particular the RCAS/Ntv-a model). The purpose of the Animal Core is to provide an animal modeling service that centralizes expertise thereby achieving uniformity and reproducibility that permits accurate comparisons between experiments, research groups, and projects in this Brain Cancer SPORE. In the current funding period, the Animal Core performed 546 experiments involving over 15,000 animals for SPORE investigators. In the next 5-year funding period, the Animal Core will continue to provide expert services to all investigators in Brain Cancer SPORE. To this end, the Core will: 1) Provide support for orthotopic animal experiments using patient-derived glioma stem cell lines (GSCs), which are currently considered the gold standard in vivo model of human gliomas. This Core has developed approximately 100 GSCs, over 40 of which have been fully molecularly characterized; 2) Provide support for flank and orthotopic animal experiments using patient-derived tumor explants from the operating room implanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice; 3) Provide support for animal experiments using immunocompetent genetically engineered mouse models (GEMMs), particularly the RCAS/Ntv-a system; 4) Provide support for orthotopic animal experiments testing oncolytic adenoviruses using immunocompetent hamster models that are permissive to viral replication; 5) Provide support for orthotopic animal experiments using traditional profession glioma cell lines from humans (U87, U251, LN229) and mice (GL261); 6) Provide support for in vivo imaging either with bioluminescence imaging (BLI) or magnetic resonance imaging (MRI) to assess efficacy of therapeutic strategies. These services are mission critical and one or more of these services are used by all Projects in this SPORE.