CORE--TRANSGENIC ANIMAL

核心C：该核心的具体目标是开发、表征和 维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相关， 提供各种年龄的动物（从胚胎到老年人）， 在这个项目中。 这个项目已经有几种转基因小鼠品系 其在所述条件下产生早老素-1（PS1）的野生型和突变形式。 血小板衍生生长因子（PDGF）B链启动子的控制。 这种启动子已在这些和其他动物中显示出驱动高效的 中枢神经系统神经元中的转基因表达。最近 对这些动物的研究表明， 功能，导致在初级神经元中产生人PS1 从这些动物中培养出来的。这一观察开启了 这些动物用于各种实验的可能性 其在本申请的其它地方详述。 转基因动物核心将有助于使动物在广泛的 不同的年龄用于个别项目。此外，定时 将适当地准备妊娠，使得初级神经元 可以产生培养物用于类似的实验用途。 在这个项目的过程中，将产生更多的动物， 将新的见解纳入早老蛋白及其 与细胞中其他过程的关系以及 老年痴呆症核心将用于描述这些转基因 小鼠在DNA，RNA和蛋白质水平，在某种程度上， 这已经在PDGF B链PS1动物中完成了。

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.