Multimodality imaging of beta-cell in anaimal models of T1DM and T2DM

T1DM 和 T2DM 动物模型中 β 细胞的多模态成像

• 批准号: 7588447
• 负责人: DANIEL KAUFMAN
• 金额: $ 18.78万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588447
• 关键词: Animal Model; Animals; Beta Cell; Biological Markers; Cell Differentiation process; Cells; Chimeric Proteins; Data; Development; Diabetes Mellitus; Diet; Embryonic Development; Fatty acid glycerol esters; Goals; Image; Imaging Techniques; Inbred NOD Mice; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans Transplantation; Life; Luciferases; Microscopy; Modality; Modeling; Monitor; Multimodal Imaging; Mus; Mutant Strains Mice; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Other Imaging Modalities; Pathogenesis; Proteins; Public Health; Range; Reporter; Reporter Genes; Research; Research Personnel; Scientist; Signal Transduction; Stem cells; Thymidine Kinase; Tissues; Transgenic Mice; Transgenic Organisms; Translations; Transplantation; abstracting; adult stem cell; cellular imaging; clinical application; design; feeding; islet; tool; transdifferentiation; type I and type II diabetes

DESCRIPTION (provided by applicant): Multimodality imaging of ss-cells in animal models of T1DM and T2DM Abstract: The expression of imaging reporter genes in ss-cells has provided powerful tools for studying ss-cell development, diabetes and islet transplantation. We have generated transgenic mice (MIP-TF mice) that express a fusion protein of three different imaging reporters (EGFP- luciferase-thymidine kinase) in their ss-cells. This should enable the longitudinal noninvasive imaging of ss-cells in the same animal by CCD and microPET, and the identification of ss-cells at the cellular level by fluorescent microscopy. The goals of this proposal are designed to provide proof-of-principle that multimodality imaging of ss-cells can augment and expedite a broad range of type 1 and type 2 diabetes mellitus (T1DM and T2DM) studies. Specific Aims: 1). Do trifusion reporter signals provide a noninvasive biomarker of the gain of ss-cell mass in MIP-TF C57Bl6 mice fed a high fat diet, a widely used model of T2DM? 2). Can the ss-cells of MIP-TF C57BL6 mice be noninvasively imaged by microPET? 3). Do trifusion reporter signals correlate with the loss of ss-cell mass during the spontaneous development of T1DM in MIP-TF NOD mice? Together, this project will; 1) enable the first microPET imaging of ss-cells in mice, which would expedite the translation of ss-cell imaging to clinical applications and; 2) enable researchers to collect ss-cell imaging data by one modality and use this data to predict the results of other imaging modalities, and equate the results with ss-cell mass. We anticipate that the data and transgenic mice that this project will generate will help other scientists to advance T1DM and T2DM research on a broad number of fronts, including studies of ss-cell development, ss-cell mass during diabetes pathogenesis, stem cell differentiation into ss-cells, transdifferentiation, and islet survival after transplantation. PUBLIC HEALTH RELEVANCE Laypersons abstract: We have generated transgenic mice that express a protein in their ss-cells that should enable researchers to image ss-cells in living animals by three different imaging techniques, allowing researchers to monitor ss-cells in living animals and at the cellular level in tissue sections. It is expected that this animal model will expedite a broad range of diabetes research, including studies of ss-cell development, embryonic and adult stem cell differentiation into ss-cells, transdifferentiation, islet transplantation and islet imaging.

描述(申请人提供)：T1 DM和T2 DM动物模型中SS细胞的多模式成像研究摘要：SS细胞中成像报告基因的表达为研究SS细胞发育、糖尿病和胰岛移植提供了强有力的工具。我们已经产生了转基因小鼠(MIP-TF小鼠)，在它们的ss细胞中表达三种不同成像报告(EGFP-荧光素酶-胸苷激酶)的融合蛋白。这应该能够通过CCD和microPET对同一动物的SS细胞进行纵向非侵入性成像，并通过荧光显微镜在细胞水平上识别SS细胞。这项提案的目的是提供原则证明，即SS细胞的多模式成像可以增强和加快广泛的1型和2型糖尿病(T1 DM和T2 DM)研究。具体目标：1)。三融合报告信号是否为喂养高脂饮食的MIP-TFC57BL6小鼠的ss细胞质量增加提供了一个非侵入性的生物标记物？MIP-TFC57BL6小鼠的SS细胞能否通过microPET进行无创性成像？三融合报告信号是否与MIP-Tf NOD小鼠T1 DM自发发展过程中ss细胞质量的丧失相关？总而言之，该项目将：1)在小鼠中实现对SS细胞的第一次microPET成像，这将加速SS细胞成像向临床应用的转化；2)使研究人员能够通过一种方式收集SS细胞成像数据，并使用这些数据来预测其他成像方式的结果，并将结果等同于SS细胞质量。我们预计，该项目将产生的数据和转基因小鼠将有助于其他科学家在广泛的前沿推进T1 DM和T2 DM的研究，包括SS细胞发育、糖尿病发病机制中的SS细胞质量、干细胞向SS细胞的分化、转分化和移植后胰岛存活的研究。与公共健康相关的普通人摘要：我们已经培育出了在其ss细胞中表达蛋白质的转基因小鼠，这应该使研究人员能够通过三种不同的成像技术对活着的动物中的ss细胞进行成像，从而使研究人员能够在活动物和组织切片的细胞水平上监测ss细胞。预计该动物模型将加速广泛的糖尿病研究，包括SS细胞发育、胚胎和成人干细胞分化为SS细胞、转分化、胰岛移植和胰岛成像的研究。