Preclinical Models of Digestive Diseases

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The main objectives of the Preclinical Models of Digestive Diseases Core are to provide VDDRC investigators with access to non-invasive small animal imaging, novel conditionally immortalized murine gastrointestinal epithelial cell lines, state-of-the art research immunohistochemistry, and consultative services in interpretation of morphologic findings in animal models and human digestive diseases. The core has three components: the Preclinical Imaging Subcore, the Novel Cell Line Development Subcore and the Tissue Morphology Subcore. The expansion and modification of this Core now provides VDDRC investigators the opportunity to move nimbly from investigations utilizing non-invasive molecular imaging (Preclinical Imaging Subcore) and histology (Tissue Morphology Subcore), often in tandem, in tractable transgenic model systems of digestive diseases (Novel Ceil Lines Subcore) to mechanistic studies using novel cell culture-based systems. In vitro studies that employ conditionally immortalized transgenic cell lines will subsequently inform and guide new in vivo experimentation which will ultimately culminate in studies of clinical populations. New services will include access to a variety of molecular imaging probes specifically tailored for imaging GI disease in preclinical animal models, including NIR-based optical imaging reagents and translational imaging compounds labeled with positron emitting isotopes (PET). The Preclinical imaging Subcore will support all major small animal imaging modalities including optical, SPECT, and PET methods for molecular imaging, as provided by the Center for Small Animal Imaging within the Vanderbilt University institute of Imaging Science. The Novel Cell Line Development Subcore provides a unique service in developing conditionally immortalized epithelial cell lines from the different segments of the gastrointestinal tract of transgenic mice with gene deletions known to be associated with known gastrointestinal pathologies. This subcore addresses the lack of normal epithelial cell lines derived from intestinal mucosa by utilizing a novel transgenic mouse, the "Immortomouse," which carries a temperature-sensitive mutant of the SV40 large T gene, an immortalizing gene active only at the permissive temperature. The Tissue Morphology Subcore provides research immunohistochemistry services for both human and animal intestinal tissue. In addition, Dr. Washington, the core Director, provides the necessary expertise for interpretation of the histologic findings obtained in these studies.