Optimisation of Transgene Expression in the Mammary Gland

Abstract

Classical animal breeding regimes rely on the importation of genes by cross-breeding and are therefore limited to those traits already present within a given species. The development of gene transfer technology which enables the generation of transgenic animals an animal that carries integrated sequences of cloned DNA in its genomeallows these limitations to be overcome. Firstly, the introduced DNA can be derived from species other than the host and, secondly, it can be modified in vitro prior to being introduced into the germline. It has been proposed that transgenesis may allow the generation of farm animals with altered phenotype (e.g. enhanced growth rate), animal models for research and animal bioreactors. It is this last opportunity which has seen the most progress over the last decade, with the expression of a variety of proteins having been targeted to milk of sheep, cattle, pigs, goats and rabbits (Wilmut and Whitelaw, 1994). Indeed, this application of gene transfer in livestock is fast approaching commercial success, with the first products currently in clinical trials. Research in this topic has been focused on two aspects: the optimisation of transgene expression and the development of methods of DNA introduction. This presentation is primarily concerned with the former but will briefly describe recent advances at the Roslin Institute which concern the development of cell culture based approaches for the generation of transgenic large animals. It should be noted, that in the context of optimising