Preclinical Models of Digestive Diseases

消化疾病核心临床前模型的主要目标是为VDDRC研究人员提供非侵入性小动物成像、新的条件永生化小鼠胃肠道上皮细胞系、最先进的研究免疫组织化学以及解释动物模型和人类消化疾病的形态学结果的咨询服务。该核心包括三个组成部分：临床前成像亚核、新型细胞系发展亚核和组织形态亚核。这一核心的扩展和修改现在为VDDRC的研究人员提供了机会，可以灵活地从使用非侵入性分子成像(临床前成像亚核)和组织学(组织形态亚核)的研究，通常是在易于处理的消化疾病转基因模型系统(新颖的Ceil Lines亚核)中进行的研究，转移到使用新的基于细胞培养的系统的机械性研究。使用条件永生化转基因细胞系的体外研究随后将为新的体内实验提供信息和指导，最终将在临床人群研究中达到顶峰。新服务将包括获得各种专门为在临床前动物模型中对胃肠道疾病进行成像而量身定做的分子成像探针，包括基于近红外的光学成像试剂和标记有正电子发射同位素(PET)的翻译成像化合物。 临床前成像分核心将支持所有主要的小动物成像方式，包括分子成像的光学、SPECT和PET方法，由范德比尔特大学成像科学研究所内的小动物成像中心提供。新的细胞系开发亚核提供了一种独特的服务，可以从已知与胃肠道疾病相关的基因缺失的转基因小鼠的胃肠道不同部分培养条件永生化的上皮细胞系。这个亚核心通过利用一种新的转基因小鼠“不朽鼠”来解决缺乏来自肠粘膜的正常上皮细胞系的问题，这种转基因小鼠携带SV40大T基因的温度敏感突变体，这种永生基因只在允许的温度下活跃。组织形态分核心为人类和动物的肠道组织提供研究免疫组织化学服务。此外，华盛顿博士，核心主任，提供必要的专业知识来解释在这些研究中获得的组织学发现。

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.