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

基本信息

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
项目类别：
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

项目摘要

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.