Mouse embryonic stem (ES) cells inaugurated a new era for mouse geneticists, by allowing them to mutate specific genes and also produce mice carrying large genomic transgenes. If it were possible to manipulate the rat genome in a similar manner through rat ES cells, the powerful database of rat physiology and behavior could be exploited to produce transgenic models of human disease. The Phase I research project demonstrated the feasibility of deriving ES cell lines from rats through development of methods for obtaining sources of ES cell precursors, tissue culture procedures, and in vitro and in vivo methods to assess the developmental potential of cell lines. For the Phase II project, these methods will be applied to further assess the two cell lines derived in the Phase I project and to rapidly analyze new candidate lines. The goals of the Phase II project are: to produce a germ-line competent rat ES cell line; to develop transfection techniques for the cells; and to use the cells to begin production of a rat model for AIzheimer's disease, with a new YAC transgenesis method developed at GenPharm.
