Transmission of the Embryonic Stem Cell (ESC) Genome to Offspring and Sexual Development in Chimeric Mice From a

Abstract: This study was performed to determine the capability of embryonic stem (ES) cells at late passage number to form functional germ cells and to orientate the sexual development of chimeric mice produced from ES cell injection into embryos. When an R1 ES cell line was routinely cultured on mitotically inactivated feeder cells in culture medium supplemented with leukemia inhibitory factor (LIF), the colonies maintained an undifferentiated ideal ES cell morphology. When the ES cells were injected into 45 eight-cell embryos, 38 embryos (84%) combined with ES cells. Twenty-eight percent of the embryos transferred to recipients developed to term. Thirty percent of offspring born were chimeric. In these chimeric individuals the contribution of ES cells to the coat was about 70 % and 99% in two male and one female chimeras, respectively. Furthermore, ES cells contributed to the germ line in the female chimera whereas they did not contribute to the germ line in two male chimeras. This study showed that female chimeras may result from injected embryos with the male ES cell and may transmit the ES cell genome to their offspring. Key Words: Mouse, ES cells, chimera, sex conversion, germ cells