The int genes in mouse mammary tumorigenesis and in normal development

In mice, the mouse mammary tumour virus causes tumours by insertional activation of host cell oncogenes. By the application of transposon tagging techniques, several cellular oncogenes, called int, have been discovered. The int-1 gene encodes a cysteine-rich protein with a signal peptide, suggesting that it may act as an extracellular growth or differentiation factor. Normally, the int-1 gene is expressed in early embryogenesis of the mouse, in particular in the developing nervous system. The essential role of int-1 in embryogenesis is underscored by its high degree of homology with the Drosophila segment polarity gene wingless, a gene involved in pattern formation in segments of the developing fly. In Drosophila, the int-1/wingless gene appears to encode a secreted factor, as concluded from antibody staining experiments. The int-4 gene is not yet fully characterized at the molecular level. From its expression pattern, however, we have concluded that int-4 may also act in the control of embryogenesis: the gene is expressed only during specific time intervals in mouse embryos and it is highly conserved in evolution.