NOVEL MRI STUDY--NEURONAL LOSS IN TRANSGENIC MICE

新颖的 MRI 研究——转基因小鼠的神经元损失

• 批准号: 2002095
• 负责人: JIA-HONG GAO
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2002095
• 关键词: Alzheimer's disease; aging; apolipoprotein E; clinical research; disease /disorder model; genetically modified animals; human genetic material tag; laboratory mouse; magnetic resonance imaging; model design /development; neural degeneration

Alzheimer's disease (AD) is an age-related illness that occurs in almost 50% of peopls over 80 years old. The hallmarks of AD include specific abnormalities in brain structures. Particularly, biomedical magnetic resonance imaging (MRI) has demonstrated a significant loss of gray matter in AD patients. However, the exact mechanism of this cerebral atrophy in AD remains unknown. This project will address this problem. Our goal of understanding the structural changes in AD will be addressed by combining expertise in three research areas; state-of-the-art microscopic MRI, tissue segmentation, and mouse genetic engineering. The integration of these techniques for animal modeling of Alzheimer's disease will promote the understanding of the neuronal progression in this disease and lead to early diagnosis. Based on the evidence that presence of the E4 allele of apolipoprotein E. (APOE)) significantly correlates with the risk of an individual developing AD, we hypothesize that MRI will show cerebral atrophy in brains of transgenic mice carrying the human APOE4 allele. It is expected that this will occur at a stage before behavioral analysis of cognitive capabilities shows abnormalities. Four groups of mice will be imaged using MRI. Three groups are the transgenic mouse lines carrying and expressing human APOE, 2, 3, and 4 genes, respectively, and one group is composed of nontransgenic age-matched controls. Each group will have twenty mice. The imaging experiment will be repeated at one-month intervals throughout the aging process. All MR images of mice brains will be segmented into gray matter (GM) and white matter (WM) images by a fuzzy classifier method. The mean and standard error of the GM and WM will be calculated for each group. An ANOVA statistical analysis will be performed on the images at each age to determine the GM and WM volume difference and to assess the statistical significance for these four groups. The relationship between changes in structure and age will be determined. The results from this transgenic animal model study will provide a means to characterize the development of Alzheimer's disease (neuronal destruction and cognitive decline) which may result from the APOE allele interactions.

阿尔茨海默氏病（AD）是一种与年龄有关的疾病，几乎发生 80年以上的人中有50％。 广告的标志包括特定 大脑结构异常。 特别是生物医学磁性 共振成像（MRI）已显示出灰质的重大损失 在广告患者中。 但是，这种大脑萎缩的确切机制 广告仍然未知。 该项目将解决此问题。 我们了解广告结构变化的目标将由 在三个研究领域结合专业知识；最先进的显微镜 MRI，组织分割和小鼠基因工程。 整合 这些针对阿尔茨海默氏病动物建模的技术将促进 对这种疾病中神经元进展的理解，并导致 早期诊断。 基于证据表明E4等位基因的存在 载脂蛋白E.（APOE））与 个人开发AD，我们假设MRI将显示大脑 携带人ApoE4等位基因的转基因小鼠大脑中的萎缩。 它 预计这将在行为分析之前的阶段发生 认知能力表现出异常。 四组老鼠将是 使用MRI成像。 三组是携带的转基因小鼠线和 分别表达人apoe，2、3和4个基因，一组是 由非转基因年龄匹配的对照组成。 每个小组都会有 二十只老鼠。 成像实验将在一个月内重复 在整个老化过程中的间隔。 小鼠大脑的所有MR图像都将 通过模糊分割成灰质（GM）和白质（WM）图像 分类器方法。 GM和WM的平均值和标准误差将为 为每个组计算。 将进行方差分析统计分析 在每个年龄段的图像上确定GM和WM体积差异，并且 评估这四组的统计意义。 这 结构变化与年龄之间的关系将得到确定。 这 这项转基因动物模型研究的结果将为 特征是阿尔茨海默氏病的发展（神经元破坏 和认知下降）可能是由APOE等位基因相互作用引起的。