Description: The original application included two scientific cores, whose functions are combined into one core for this application. The aims of this core are five-fold. 1. The core will support the isolation and sequencing of mouse genes necessary for the different projects. 2. The core will be responsible for performing gene targeting experiments in ES cells. 3. The core will support the generation of transgenic mice by the pronuclear microinjection of DNA and by the injection of ES cells that have been targeted by homologous recombination. 4. The core will support the housing of the mice used by the different projects. 5. The core will support advanced imaging techniques using a confocal laser scanning microscope, a two-photon excitation microscope, and an image analysis workstation. By providing support for different aspects of gene cloning and sequencing, gene targeting, transgenic production and housing, and advanced image analysis, this core will serve as a key resource for all the projects in this program. It is stated that these different resources and services will be provided through a single core in order to minimize the administrative overhead required of each additional core and to enable the financial resources of this core to be shifted rapidly to different uses as scientific priorities change.