In next 5-year funding period, investigators in Brain Tumor SPORE will continue to utilize the expert services provided by the Animal Core. The majority of projects in the SPORE rely on intracranial (orthotopic) implantation of established, adherent glioma cell lines, which are molecularly well characterized. Improvements in modeling the human disease will be achieved through the use of orthotopic xenografts of human glioma stem cells (GSCs), which are an important component of solid tumors, better replicate the human disease, and may mediate treatment resistance. These patient-derived GSC cell lines (N>50 to date) have been molecularly characterized into proneural, mesenchymal, classical and neural subtypes. In addition, genetically engineered mouse models of glioma (GEMMs) such as the RCAS/Ntv-a system are utilized by SPORE investigators. Specific genes of interest important for tumorigenesis can be evaluated in this model in a cell-type specific manner. Other GEMMs available within the Animal Core include: hGFAP-Cre*;p5S '?'^?'';Pten '?^^ and Nestin-CreERT2 clnk4a/Arf UL cPTEN UL GFAP-tta tet- EGFRviil. Importantly, tumors generated in immunocompetent mice allow for better evaluation of interactions between tumor and the native microenvironment. Finally, we will continue to maintain and provide assistance with the establishment of traditional xenograft models from standard glioma cell lines (e.g. U87, U251, LN229, etc.).
The Specific Aims of the Animal Core are:
Aim 1 : Provide support for animal experiments using patient derived glioma stem cell lines (GSCs) as orthotopic xenografts in immunodeficient mice.
Aim 2 : Provide support for animal experiments using Genetically Engineered Mouse Models (GEMMs).
Aim 3 : Maintain working stocks of cell lines.
Aim 4 : Provide support for xenografts of standard glioma cell lines.
DO NOT EXCEED THE SPACE PROVIDED. Three of the four Brain Turiior SPORE projects are expected to use significant numbers of mice for their experiments. The Brain Tumor Animal Core will provide expert oversight of the animal experiments. Experienced personnel will execute the experimental plans.
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