LOCALIZATION OF LARGE-T ONCOPROTEIN DURING THE EMBRYONIC AND FETAL DEVELOPMENT OF TRANSGENIC MICE

Oncoproteins are not only involved in the development of tumors but al so play a role in physiological regulation in embryonic growth and dif ferentiation. The mechanisms by which regulation is accomplished in em bryonic stages differ from postnatal or adult stages. Oncoproteins res ponsible for tumors in the adult, i.e., products of proto-oncogenes, a re prevented from causing tumors in the embryo. If oncogenes are intro duced artificially into the embryo, will they be governed by the embry onic regulation described above? To answer this question we used trans genic mice in which the hybrid construct MSV-SV40-large-T, composed of the Simian-Virus-Oncogene-Large-T with its SV40-promotor and the Molo ney Murine Sarcoma Virus (MSV)-enhancer, had been integrated. Under th e influence of large-T expression, these animals develop either brain or endocrine pancreas tumors. In the present investigation, we localis ed large-T expression during development of mouse embryos and fetuses. Interestingly, we saw large-T positive reactions in organ anlagen oth er than those that later develop tumors. We found large-T antigens in cartilage anlagen, e.g., in ribs and vertebrae, particularly in fetuse s of days 14 to 17, and also in a variety of epithelial cells such as in the lung or the choroid plexus. Our results indicate that, as for p roto-oncogene products, the effect of an artificially introduced trans genic oncogene product can also be regulated by embryonic cells. (C) 1 997 Wiley-Liss, Inc.