Cell Growth & Differentiation, Vol 4, Issue 11 891-900, Copyright © 1993 by American Association of Cancer Research
H-2/myc, E mu/myc, and c-myc transgenic mice: potent sources of early hematopoietic cell lines
J Roland and D Morello
Department of Immunology, Institut Pasteur, Paris, France.
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.