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.
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