Abstract
Mouse teratocarcinoma stem cells cultured in vitro provide the unique prospect of obtaining new strains of mice with genetic changes that have been predetermined, preselected, and precharacterized. This possibility rests upon the demonstrated capacity of the stem cells, after injection into blastocysts, to produce lineal cell descendants that are functional gametes. Thus far, only one in vitro line of teratocarcinoma cells has been founa capable of forming germ cells in vivo. The line, established in this laboratory from a 129 (agouti‐strain) embryo, was designated METT‐1 and was shown in previous reports to be karyotypically normal and chromosomally female (X/X); after introduction of the cells into C57BL/6 (non‐agouti‐strain) blastocysts, one mosaic‐coat female (out of nine that were test‐mated) had some offspring from the teratocarcinoma cell source. We report here results from an extension of this study. The new series was initiated in part to clarify the frequency of mosaic individuals with some reproductive cells of the tumor strain, as an indication of the practicability of the proposed genetic manipulation experiments. From among the first eight mice produced, a single female with a mosaic coat was test‐mated to a C57BL/6 male and produced progeny. An agouti (dominant‐color) 129‐derived male appeared in her second litter. The teratocarcinoma lineal provenance of this F__1__ animal was confirmed by its heterozygosity for the hemoglobin electrophoretic variants (Hbb locus) due to the 129 (diffuse‐type) and C57BL/6 (single‐type) strains. Thus, in our two series combined, the METT‐1 cell line has given rise to normal germ‐line progeny in a substantial frequency (2/10, or 20%) of tested females.