GENE AND TRANSGENE REGULATION IN THE DEVELOPING MOUSE

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Our laboratory continues to investigate mechanisms of gene control in the mouse, using a variety of approaches. The first of these concerns the expression of distinct homeobox genes in the developing embryo. We find that Hox 1.1 and Hox 1.5 are differentially expressed and that their expression coincides with specific events of pattern formation during midgestation. Another of our studies deals with the action of an oncogene, a protooncogene and a DNA replication factor, respectively, in the lens of transgenic mice. We find that each of these factors affects cell growth in vivo in a distinct way. We also find that transgene mediated cell transformation in vivo is a new and powerful way of immortalizing highly specialized cell systems such as the lens cell. The part of the project that addresses the human AIDS disease has produced an unsuspected finding. Of all cell systems in the transgenic mouse able to activate the HIV LTR, the Langerhans cell of the skin appears the most powerful. This enforces the view of strong macrophage involvement in AIDS pathogenesis. In another experiment of biomedical importance, we have shown transgenic animals to be a potential source for human proteins of therapeutic value. We have generated mice that produce large amounts of tissue plasminogen activator in their milk. This protein is used for treatment of clotting disorders. The final study of this report concerns tissue specific expression of murine P450 genes. In situ analysis of expression of Pl and P3, two distinct P450 genes, has pointed out specific cell systems involved in the control of smoking and other environmental noxes.