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）小鼠系 （细胞系C3-3和E1 -2），其表达突变的人源化淀粉样蛋白前体蛋白 (APP)（Mo/Hu-APPswe），其水平足以诱导B-淀粉样蛋白（AB）沉积 年龄在20到24个月之间。这些动物已交配C57 BL/6 J小鼠 经10代传代，获得同源动物（99.99%）。在项目1中， 建议进行行为测试（Morris水迷宫，八臂放射状迷宫， 和Y-迷宫），旨在检查他们的同类/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-、24-、25- 和28个月大）将被人为地处死以提供组织， 详细的神经病理学/神经化学评价（项目2）。我们一起努力， 这些研究将确定认知能力的变化 与特定的神经病理学/神经化学异常相关。的 一项计划中的研究将首次对突变APP进行行为学表征， 在单一近交系背景上是同源的Tg小鼠，并且将是 第一次证实了两个独立的小鼠品系的发现， 相似水平的突变型APP，并在相似的年龄发展AB沉积物。到 探讨AB沉积与认知能力的关系， 计划将Tg E1 -2和C3-3小鼠彼此交配以获得双Tg动物 会在年轻时出现AB型沉积和相关的异常。 这些队列将进行盲法测试，然后处死， 神经病理学/神经化学分析（数据由项目2提供）。 最后，第三系Mo/Hu-APPswe小鼠（系Q2-2），其表达M-APPswe基因。 转基因水平略低于诱导AB沉积所需， 进行行为学和神经病理学/神经化学分析。他们的 计划的小鼠行为表征，以及 在项目2中提出的神经病理学/神经化学研究，将使他们 确定（在核心B的统计分析的帮助下） APP高表达、AB肽合成和AB沉积对 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.