H-2/myc, E mu/myc, and c-myc transgenic mice: potent sources of early hematopoietic cell lines.

Activation of the cellular c-myc oncogene appears to be linked to the development of malignancies in a variety of tissues, in particular, hematopoietic tumors. In an attempt to obtain cell lines corresponding to early stages of lymphoid differentiation, we have derived several strains of transgenic mice in which human c-myc genomic sequences were coupled to various regulatory sequences, H-2, E mu, and c-myc. The class I H-2Kb 5' region is active in most adult tissues; the activity of the enhancer E mu of the heavy chain immunoglobulin is restricted to lymphocytes; and the 2-kilobase-long c-myc 5' region has been shown by in vitro experiments to contain most of the sequences required for c-myc regulated expression. Regardless of the construct, H-2/myc, E mu/myc, or c-myc, the transgenes were mainly expressed in lymphoid tissues. However, the quantity of transgene mRNA differed markedly among the transgenic strains, thus providing a situation in which the level of c-myc expression could be correlated with tumor development. Several cell lines were derived and maintained by in vivo transplantation and/or in vitro cultures. All except two of the lines correspond to immature T- or B-lymphoblasts, as revealed both by fluorescence-activated cell sorting and Southern blot analysis; one cell line corresponds to a gamma delta T-cell population, and the other to a bipotential mixed lymphoid and myeloid tumor.