Myc family oncogenes share a similar gene organization, encode DNA binding nuclear phosphoproteins, possess similar oncogenic activities, and are expressed in a distinctive temporal and spatial manner during normal murine development. The differential or coordinate expression of myc family genes may influence the processes leading to cellular commitment and differentiation. To better understand the biological functions of myc family oncogenes in mammalian development, Dr. DePinho will characterize the developmental role of c-, N-, L-myc gene products in several well defined in vitro differentiation systems and in the developing mouse embryo. In vitro systems he will examine the biological impact of forced or absent myc expression on cellular differentiation. Altered myc activity will be achieved with the help of constitutive myc expression constructs and with the help of inducible antisense constructs. To study the normal role of myc in the developing animal, Dr. DePinho will produce mice which are inactive at both L-myc alleles. Gene disruption will make use of homologous recombination and embryonic stem cell techniques to produce germ line chimeras. The experiments proposed will provide further insight into the biological significance of c-, N-, and L-myc in normal mouse development. %%% Genes, called oncogenes, were first discovered due to their ability to cause transformation to malignant phenotypes in cultured cells.. These genes have since been shown to be involved in the normal development of an embryo. This study proposes to determine what the role of one of these gene families plays in normal development.
