TRANSGENIC AND KNOCKOUT ANIMAL CORE

该核心将维持现有的转基因（和其他）小鼠系，并将为该计划内的项目提供不同年龄的动物（从胚胎到老年）。该中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。项目1将使用转基因表达野生型和突变型PS1的动物，发育中表达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）来检查对其他γ -分泌酶成分（aph-1， pen-2和nicastrin）水平和稳定性的影响。在项目3中，这些动物将被用来研究这些转基因对APP和Notch作为γ -分泌酶底物之间竞争的影响，以及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，这些动物将被用来评估每种蛋白质对其他γ分泌酶底物切割的贡献。其他转基因的设计和生成将与项目6 （APLP1和APLP2）合作，并可能与项目5 （Nectin-1）合作。此外，还将根据需要为调查人员提供畜牧业服务。通过整合涉及动物的工作，该项目力求通过协调不同研究人员的要求并在可能的情况下共享动物，有效地利用小鼠。这将有助于保持动物数量和成本尽可能低，同时确保在种群空间的限制下，满足所有项目调查人员的需要。本中心的动物也尽可能提供给项目外的研究人员使用。

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.