Assessing memory in mouse models of Alzhiemer's disease

描述：(改编自应用程序) 这些应用已经产生了两个独立的转基因(TG)小鼠品系 (品系C3-3和EL-2)表达突变的人源性淀粉样前体蛋白 (APP)(Mo/Hu-APPswe)水平足以诱导B-淀粉样蛋白(AB)沉积 年龄在20到24个月之间。这些动物已经与C57BL/6J小鼠交配 10代获得同源动物(99.99%)。在项目1中，他们 建议进行行为学测试(Morris水迷宫，八臂径向迷宫， 和Y-迷宫)，旨在检查他们的同源基因/TG的认知能力 Mo/Hu-APPswe小鼠。在行为测试之后，每个队列(6-，14-，22- 和28个月大)将被人类牺牲以提供纸巾 详细的神经病理/神经化学评估(项目2)。一起， 这些研究将确定认知能力的变化 与特定的神经病理/神经化学异常相关。这个 计划中的研究将首次对突变的APP进行行为特征描述 在单一近交系背景上是同源的转基因小鼠，并将成为 首先确认两个独立的小鼠品系的研究结果 类似水平的突变APP和开发年龄相似的AB矿藏。至 探索AB沉积与认知能力的关系，他们 计划将Tg EL-2和C3-3小鼠相互交配以获得双TG动物 这将在更年轻的时候形成AB矿床和相关的异常。 这些队列将被盲目测试，然后被牺牲 神经病理学/神经化学分析(数据由项目2提供)。 最后，第三个Mo/Hu-APPswe小鼠品系(Q2-2)表达 转基因水平略低于诱导AB沉积所需的水平，将 进行行为和神经病理学/神经化学分析。他们的 小鼠有计划的行为特征，以及 在项目2中提出的神经病理学/神经化学研究将允许他们 (在核心B的统计分析的协助下)确定 APP高表达、AB肽合成和AB沉积对细胞周期的影响 小鼠的认知能力。

DESCRIPTION: (Adapted from the application) The applications have generated two independent lines of transgenic (Tg) mice (lines C3-3 and El-2) that express mutant humanized amyloid precursor protein (APP) (Mo/Hu-APPswe) at levels sufficient to induce B-amyloid (AB) deposition between 20 and 24 months of age. These animals have been mated C57BL/6J mice for ten generations to obtain congenic animals (99.99%). In Project 1, they propose to conduct behavioral tests (Morris water maze, eight-arm radial maze, and Y-maze) designed to examine the cognitive abilities of their congenic/Tg Mo/Hu-APPswe mice. Following behavioral testing, each cohort (6-, 14-, 22- and 28 months of age) will be humanly sacrificed to provide tissues for detailed neuropathological/neurochemical evaluations (Project 2). Together, these studies will determine whether changes in cognitive performance correlate with specific neuropathological/ neurochemical abnormalities. The planned study will, for the first time, behaviorally characterize mutant APP Tg mice that are congenic on a single inbred strain background and will be the first to confirm findings of two independent lines of mice that express similar levels of mutant APP and develop AB deposits at similar ages. To explore the relationship between AB deposition and cognitive ability, they plan to mate Tg El-2 and C3-3 mice to each other to obtain double-Tg animals that will develop AB deposits and associated abnormalities at younger ages. These cohorts will be tested blindly and then sacrificed for neuropathological/neurochemical analysis (data provided by Project 2). Finally, a third line of Mo/Hu-APPswe mice (line Q2-2), which expresses the transgene at levels slightly less than required to induce AB deposition, will be behaviorally and neuropathologically/neurochemically analyzed. Their planned behavioral characterization of the mice, together with the neuropathological/neurochemical studies proposed in Project 2, will allow them to determine (with assistance in statistical analyses from Core B) the influence of APP hyper expression, AB peptide synthesis, and AB deposition on the cognitive abilities of mice.