Proto-oncogenes are thought to play key roles in regulating cellular proliferation and differentiation, both during embryonic development and in the adult. These genes encode proteins with diverse biochemical functions including growth factors, receptors, nucleotide binding proteins, protein kinases, and transcription factors. These molecules appear to be the major regulatory components of cellular signal transduction networks. It follows that mutations arising in proto-oncogenes could contribute to cancer and other diseases by disrupting the normal signaling pathways in the cell.

Transgenic technology enables us to manipulate proto-oncogenes within the context of the mouse genome. This has allowed us to create animal models of known human genetic diseases and to study the function of genes whose involvement in cancer is suspected. Using strategies such as homologous recombination in mouse embryonic stem cells and DNA microinjection of mouse embryos, our laboratory is generating transgenic mice designed to determine the in vivo function of genes encoding protein-tyrosine kinases. We are also using the zebrafish as another vertebrate model system for examining the function of genes encoding protein-tyrosine kinases. We have cloned a number of zebrafish tyrosine kinase-encoding genes and are currently examining their expression patterns during embryogenesis.