TRANSGENIC MOUSE CORE

转基因小鼠核心(核心C)将满足以下组成部分项目的转基因小鼠需求 这个PPG。这种转基因小鼠核心的主要原理是确保单个项目有一个 以经济有效和高效的方式提供一致和可靠的计划转基因小鼠品系。 转基因小鼠群体将保留在Taconic实验室，以确保小鼠可用于 任何学术实验室，在没有费用和延迟卫生/检疫要求的情况下转移小鼠 在学术机构之间。这一点尤其重要，因为核心C将为4个学术机构提供服务。 核心C将通过三个具体目标实现这些功能： 具体目标1：按照PPG的要求，协调在Taconic建立转基因菌株。 1.1在Taconic协调存放目前可从项目负责人那里获得的五个转基因小鼠品系 和合作者。此外，项目1(LaDu)目前在Taconic维护五个转基因菌株，这些转基因菌株 准备好供PPG使用。具体的菌株和来源在图1和表1中列出。 初步数据中描述了菌株。 1.2监督核心B产生的新转基因品系(ApoER2-TG和LDLR-TG)的及时转移 (BU，华盛顿大学鼠标遗传学核心设施)至Taconic。 1.3在PDGF-APP-TG小鼠与ApoER2-TG、ApoER2-KO、LDLR-TG、LDLR-KO、 MLRP-TG、mLRP-KO、LDLR-TG、LDLR-KO，得到6个新的转基因菌株。 分目标1.2和1.3中提到的这8个新的转基因菌株在设计一节中进行了描述。Dr。 Weeber(项目5)将对这些菌株进行行为和神经可塑性表征。 具体目标2.确保为该方案提供所要求的成年和定时怀孕动物 项目。上述18个转基因品系的小鼠选育和菌落维持 野生型小鼠，将需要一个系统的方法，导致在核心C 工作人员和Taconic合作者，包括项目预测的动物使用量的季度更新和- 适应繁殖策略。这将确保及时向各项目供应MICE。 通过监督Taconic和项目之间的所有鼠标活动，Core C将帮助最大化 有价值的转基因小鼠资源的试验性利用。 具体目标3.使PPG产生的转基因菌株可供更广泛的科学界使用。 这种方法明显的“创新”或“外在优点”是，根据美国国立卫生研究院的指导方针，所有 作为该计划的一部分开发的转基因小鼠品系将可用于一般研究 社区。由PPG及其项目负责人开发的新MICE可以免费存放在 阿尔茨海默病小鼠模型中心(杰克逊实验室)。

The Transgenic Mouse Core (Core C) will service the transgenic mouse needs of the component projects of this PPG. The primary rationale for this transgenic mouse core is to ensure that individual projects have a consistent and reliable source of planned strains of transgenic mice in a cost-effective and efficient manner. The transgenic mouse colonies will be maintained at Taconic labs to ensure that the mice will be available to any academic lab without the expense and delay of the health/quarantine requirements for the transfer of mice between academic institutions. This is particularly important, as Core C will serve 4 academic institutions. Core C will achieve these functions via three specific aims: Specific Aim 1: Coordinate establishing transgenic strains at Taconic as required by the PPG. 1.1 Coordinate depositing at Taconic the five transgenic mouse strains currently available from Project leaders and collaborators. In addition, Project 1 (LaDu) currently maintians five transgenic strains at Taconic that are ready for use by the PPG. The specific strains and sources are listed in Figure 1 and Table 1. These 10 strains are described in Preliminary Data 1.2 Oversee the timely transfer of the new transgenic lines (ApoER2-Tg and LDLR-Tg) generated by Core B (Bu, Washington University Mouse Genetics Core facility) to Taconic. 1.3 Generate the crosses between PDGF-APP-Tg mice and ApoER2-Tg, ApoER2-KO, LDLR-Tg, LDLR-KO, mLRP-Tg, mLRP-KO, LDLR-Tg, LDLR-KO, resulting in six new transgenic strains. These 8 new transgenic strains referred to in sub-aim 1.2 and 1.3 are described in the Design Section. Dr. Weeber (Project 5) will perform behavioral and neuroplasticity characterization of these strains. Specific Aim 2. Ensure availability of requested adult and timed pregnant animals for the program projects. Mouse breeding and colony maintenance of the 18 transgenic strains described above as well as wild type mice, will require a systematic approach resulting from regular communication between the Core C staff and the Taconic collaborators, including quarterly updates of projected animal use by the projects and on- going adaptations to the breeding strategies. This will ensure the timely supply of mice to the various projects. By overseeing all mouse activity going between Taconic and the projects, Core C will aide in maximizing experimental use of valuable transgenic mouse resources. Specific Aim 3. Make PPG-generated transgenic strains available to the broader scientific community. The obvious "innovation" or "extrinsic merit" of this approach is that under the NIH guidelines, all the transgenic mouse strains developed as part of this program will be available to the general research community. The new mice developed by this PPG and its project leaders can be deposited at no cost in the Alzheimer's Disease Mouse Model Center (Jackson Laboratories).