CORE--TRANSGENIC ANIMAL

核心C：这个核心的具体目标是开发、表征和 保持表达各种形式蛋白质的转基因动物 与早老素生物学和阿尔茨海默病的研究有关 提供不同年龄的动物(从胚胎到老年)给不同的 此计划内的项目。 该项目已经提供了几种转基因小鼠品系 产生野生型和突变型的早老素-1(PS1) 控制血小板衍生生长因子(PDGF)B链启动子。 这种启动子已经在这些动物和其他动物中被证明能够有效地驱动 转基因在中枢神经系统神经元中的表达。近期 对这些动物的研究表明，转基因是 功能，导致在初级神经元中产生人PS1 用这些动物准备的文化。这一观察打开了 在各种实验中使用这些动物的可能性 这些信息在申请的其他地方有详细说明。 转基因动物核心将使动物在更广泛的范围内获得 在各个项目中使用的年龄各不相同。此外，计时的 将根据情况准备妊娠，以便初级神经元 培养物可用于类似的实验用途。 在该计划的过程中，将产生更多的动物， 结合了对早老素和他们的生物学的新见解 与细胞内其他过程的关系以及在细胞发育中的作用 阿尔茨海默病。核心将用来描述这些转基因 在DNA、RNA和蛋白质水平上，以一种与之相当的方式 这已经在PDGF B链PS1动物身上完成了。

Core C: The specific aim of this core is to develop, characterize and maintain transgenic animals which express various forms of proteins relevant to the study of presenilin biology and Alzheimer disease and to provide animals of various ages (from embryos to aged adults) to various projects within this program. Already available to this projects are several lines of transgenic mice which produce wild type and mutant forms of presenilin-1 (PS1) under the control of the platelet-derived growth factor (PDGF) B-chain promoter. This promoter has been shown in these and other animals to drive efficient transgene expression in neurons of the central nervous system. Recent studies with these animals have demonstrated that the transgene is functional, resulting in the production of human PS1 in primary neuronal cultures prepared from these animals. This observation opens the possibility for use of these animals in a wide variety of experiments which are detailed elsewhere in the application. The Transgenic Animal Core will serve to make animals available at a wide variety of ages for use in individual projects. Additionally, timed gestations will be prepared, as appropriate, so that primary neuronal cultures can be generated for similar experimental use. Over the course of the program, additional animals will be generated, incorporating new insight into the biology of the presenilins and their relationship to other processes in the cell and in the development of Alzheimer disease. The Core will serve to characterize these transgenic mice at the DNA, RNA and protein levels, in a manner comparable to that which has already been done for the PDGF B-chain PS1 animals.