Production of Chimeras Derived from Murine Embryonic Stem Cells
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Embryonic stem (ES) cells are undifferentiated cells derived from early mouse embryos, which under appropriate culture conditions proliferate continuously in vitro. ES cells have been demonstrated to be pluripotent in vivo from their capacity to form teratocarcinomas and germline chimeric mice (1 –3 see Fig. 1 ), depending on the environment into which the stem cells are introduced. When ES cells are introduced under the kidney capsule, in vivo differentiation is chaotic with the teratocarcinoma composed of a wide variety of different cell types. If, however, the stem cells are returned into a preimplantation mouse embryo, in vivo differentiation proceeds in a normal and organized manner, and the ES cells colonize the three primary cell lineages of the developing embryo: the primitive ectoderm, endoderm, and mesoderm. This leads to the formation of chimeric offspring composed of cells of two different genetic constitutions: the host embryonic cells and those derived from the ES cells.
Fig. 1. A male germline chimera transmitting the dominant black agouti coat color genotype derived from the 129/Sv ES cells to all offspring, after mating with an albino MF1 female. The chimera was produced following the injection of XY stem cells into a presumed XX host blastocyst, from the albino MF1 mouse strain. The male stem cells resulted in the “sex conversion” of the mouse.
