A multicopy c-Myc transgene as a nuclear label: overgrowth of Myctg50 cells in allophenic mice.

To trace cell lineages and the origin and fate of cells in transplantation and embryo chimeras, a DNA/DNA in situ hybridization cell labelling system was developed, based on a 50-copy murine c-myc transgene on mouse chromosome 8. Elevated levels of cMyc mRNA were found in Myctg50 (Myctg50/0 and Myctg50/Myctg50) transgenic tissues, but adult transgenic NMRI mice were anatomically and histologically indistinguishable from control NMRI mice and did not develop tumours on a wild-type or nude (nu/nu) background. The hybridization label detected transgenic nuclei with an efficiency of approximately 80%. In muscle grafts, this transgene label was successfully applied to trace donor cells in a labelled host and to study the invasion of a graft by host cells. When the cMyc hybridization was used in allophenic mice of the control<-->NMRI-Myctg50/? (nu/+ or +/+) type, an up to a three-fold excess of MYCtg50 positive over control nuclei was found in all organs examined (ventricle, skeletal muscle, liver, small intestine). This overgrowth of MYCtg50 cells is probably due to transgene expression. Four out of seven (C57BL/6xBALB/c) or (C57BL/6xNMRI)<-->MYCtg50 allophenic mice displayed anatomical abnormalities, e.g. an enlarged thymus and a tumour in the groin region. As these abnormalities were only observed in allophenic mice, they might be due to the imbalance of growth potential between MYC*tg50 transgenic and normal cells in the same individual.