ONDCOGENESIS AND INSERTION MEDIATED MUTAGENESIS IN TRANSGENIC MICE

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Our laboratory investigates mechanisms of gene control in the living mammalian organism. Specific genes are introduced by microinjection into the germ line of mice, and expression of these genes is assayed in the resulting transgenic animals. To this end, organ screens are performed at various stages of development from fetus to adult. Two problems were studied. The first dealt with oncogenesis in the transgenic animal. A fused gene, consisting of the mouse Alpha crystallin promoter and the coding sequences of the SV40 tumor antigens, was inserted in the mouse germ line. Lens tumors developed in all mouse lines generated so far. Tumor cells expressed the SV40 T antigen. The onset of cell transformation coincided with lens differentiation during mid-getation. The second problem concerns insertional mutagenesis observed in one of our strains of transgenic mice. A dominant phenotype of small litter size was shown to coincide with a chromosome 6/17 reciprocal translocation, and the gene insert was localized by in situ hybridization to one of the rearranged chromosomes.