TRANSGENIC AND KNOCKOUT ANIMAL CORE

该核心将维持现有的转基因（和其他）小鼠品系，并将为该计划内的项目提供各种年龄（从胚胎到老年人）的动物。核心还将与该项目的研究人员合作，开发与其项目相关的新小鼠品系。将在项目1中使用转基因表达野生型和突变型PS1的动物、发育表达aph-1和pen-1的动物以及缺乏PS1的动物（胚胎或神经元培养物），以检查对其他γ-分泌酶组分（aph-1、pen-2和nicastrin）水平和稳定性的影响。在项目3中，这些动物将用于研究这些转基因对APP和Notch作为γ-分泌酶底物之间的竞争以及对γ-分泌酶与其底物之间相互作用的影响。在项目5和项目6中，这些动物将用于评估每种蛋白质对其他γ-分泌酶底物裂解的贡献。将与项目6（APLP 1和APLP 2）以及潜在的项目5（Nectin-1）合作设计和产生额外的转基因。此外，将根据需要为研究者提供畜牧服务。通过整合涉及动物的工作，该计划项目寻求通过协调不同研究人员的请求并在可能的情况下共享动物来有效利用小鼠。这将有助于保持动物数量和成本尽可能低，同时确保在殖民地空间的限制内，满足所有项目中研究人员的需求。该核心的动物也尽可能提供给计划项目以外的研究者。

This Core will maintain existing lines of transgenic (and other) mice and will provide animals of various ages (from embryos to aged adults) to projects within this program. The Core will also work with investigators of the Program Project to to develop new lines of mice relevant to their projects. Animals with transgenic expression of wild type and mutant PS1, animals under development expression aph-1 and pen-1, and animals lacking PS1 (embryos or neuronal cultures) will be used in Project 1 to examine effects on the levels and stability of the other gamma-secretase components (aph-1, pen-2 and nicastrin). In Project 3, these animals will be used to study the effects of these transgenes on the competition between APP and Notch as substrates for gamma-secretase and on the interactions between gamma-secretase and its substrate. In Project 5 and Project 6, these animals will be used to assess the contribution of each of these proteins to the cleavage of other gamma-secretase substrates. Design and generation of additional transgenics will be performed in collaboration with Project 6 (APLP1 and APLP2) and, potentially, with Project 5 (Nectin-1). Additionally, animal husbandry services will be provided for investigators as needed. By consolidation of efforts involving animals, the Program Project seeks to have efficient use of mice, through the coordination of requests from different investigators and sharing of the animals when possible. This will help to keep animal numbers and costs are kept as low as possible while ensuring that, within the limits of colony space, the needs of investigators in all projects are met. Animals from this Core are also made available, as possible, to investigators outside of the Program Project.