Lymphohematopoietic and Other Malignant Neoplasms Occurring Spontaneously in Transgenic Mice Carrying and Expressing MTV/myc Fusion Genes

Abstract

Transgenic mice carrying and expressing exogenously introduced cellular oncogenes offer the opportunity to study oncogenesis in the context of the living organism (Stewart et al., 1984; Adams et al., 1985). To this end, we have produced various strains of transgenic mice that carry a normal mouse c-myc gene in which increasingly larger portions of the myc promoter region have been replaced by a hormonally inducible mouse mammary tumor virus promoter (Stewart et al., 1984). Two of these transgenic strains were of considerable interest, since virtually all of the available female progeny, which were in their second and third pregnancies, spontaneously developed mammary adenocarcinomas of the breast (Stewart et al., 1984). It was also of interest that the MTV/myc fusion gene was expressed both in nonneoplastic and neoplastic mammary glands, and with the exception of the normal salivary gland, was not significantly expressed in any other tissue (Davis et al., 1986). In contrast, another transgenic strain, hereafter referred to as the “K” strain, expresses MTV/myc fusion gene mRNA. in a much wider range of tissues, with the subsequent development of a high spontaneous incidence of malignant neoplasms (Leder et al., 1986). Although the largest portion of malignant neoplasms are lymphoid cell neoplasms of B cell derivation, we also have observed smaller numbers of T and non-B, non-T lymphomas as well as mast cell sarcomas, testicular neoplasms of Sertoli cell type, and mammary adenocarcinomas. We have described our experience with this strain in detail elsewhere (Leder et al., 1986).

and supported in part by a grant from the Margaret Early Medical Research Trust