The Mouse Pathology and Imaging Core has been an essential part of the Thyroid Cancer P01 grant, supporting the use of mouse models for all four of the research projects. A major goal of the Core will be to provide expertise in mouse pathology with a specific focus on detailed aspects of thyroid gland pathology, including the pathobiology of mouse thyroid carcinoma. Pathology support will be provided by veterinary anatomic and clinical pathologists that are Diplomates of the American College of Veterinary Pathologists. Expertise in comparative thyroid gland pathology will enable appropriate interpretation and evaluation of the mouse models in the research projects and comparison to human thyroid cancer. The mouse clinical pathology service also includes full-service hematology and clinical chemistry analyzers in the laboratory of Dr. Krista La Perie that can appropriately analyze small blood volumes from mice. This structure will provide excellence and continuity of service for the research projects, and allow consistency and high level integration of pathologic changes observed in the various mouse models used in this project. Additionally, this core will provide state-of-the art imaging services with developed expertise in advanced modalities specific for the analysis of the thyroid gland, such as anatomic imaging using high resolution, 3D mouse thyroid ultrasonography and functional imaging using integrated microCT/microSPECT/microPET. This latter imaging is capable of analyzing the same radiotracers in mice as are used clinically in human patients with thyroid cancer, including radioiodide to assess iodide uptake and retention, and fiuorodeoxyglucose to assess metabolic activity. Additional imaging modes available through the core include digital Faxitron high resolution radiography, high resolution small animal magnetic resonance imaging (MRI), and whole animal or organ bioluminescence and fluorescence imaging. Other services that will be available to investigators include (1) technical expertise and support for the primary culture of mouse thyroid tumors;(2) support for studies on metastasis including orthotopic implantation of tumor tissue into the thyroid bed and injection of tumor cells into the tail vein and/or left cardiac ventricle to induce metastatic disease;and (3) support for the development of new transgenic and targeted alleles for novel mouse model development. Facilities will include a necropsy facility, automated immunostainers, microscopy facilities including a multi-headed microscope with video output for conferences, dedicated bioluminescent and fluorescent in vivo imaging instrumentation, dedicated high resolution/high frequency ultrasound equipment for small animals, digital gross and microscopic photography facilities, quantitative image analysis software, and mouse surgery and radiology facilities. Because the science in this project is spread among various models and physical locations, the availability of a single core to coordinate, analyze, and compare data will provide an essential resource and significantly enhance the quality and validity ofthe research data.
As tools for the identification of the molecular events that predispose to the initiation, promotion, and development of thyroid cancer and its metastasis have become more sophisticated, the requirement for physiologic models with which to study these processes has also grown. The Mouse Imaging and Pathology Core provides an integrated resource for the generation and analysis of models used to study these processes in the mouse, which is the most effective and efficient in vivo system for studying human cancer. The availability of a this core supports the overall Program Project goals not only by fostering cutting edge mouse modeling of thyroid cancer, but also by serving as a collaborative focus through which project scientists can interact in elucidating how genetic and non-genetic alterations affect all aspects of thyroid cancer biology in the living organism.
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