Teratocarcinoma derived from mouse zygotes after the introduction of activated human c-Ha-ras DNA

We attempted to produce transgenic mice harboring the normal or activated human c-Ha-ras gene in order to examine the function of activated oncogenes in tumorigenesis. During the process of development, it happened that not only normal looking fetuses were obtained but also malformants, developmentally arrested conceptuses and tumors. Six such abnormally developed embryos were found to have been integrated with the activated human c-Ha-ras gene. One of the two tumors thus obtained was formed after the injection of 6.3 kb DNA fragment containing the gene for p21 with valine at the twelfth position. This tumor was integrated with two copies of the introduced DNA at a particular site in a chromosome and arranged in tandem in a head to tail direction. Histological analysis revealed that this tumor was constructed from at least three types of cells: two originating from different germ layers (one endoderm and the other mesoderm) and the third from an extra-embryonic ectoderm. The other tumor revealed similar features. Thus, it was strongly suggested that these tumors were derived from the very early developmental stage of the embryo, and had features very similar to those of teratocarcinoma.