MAMMARY-SPECIFIC TRANSGENES AS TOOLS IN SCIENCE AND INDUSTRY (Invited Paper)

The ability to modify the animal genome by microinjection of DNA fragments into fertilized embryos was first achieved in 1980. The most abundant mammary-specific milk protein genes were recognized shortly thereafter as valuable tools with which to apply this technology to the mammary gland. The expression of the six major milk protein genes accounts for up to 80 % of the total mRNA in lactating mammary tissue. A few of these genes function efficiently as transgenes and can target the expression of heterologous gene product in a tissue-specific, developmentally regulated fashion. The use of regulatory DNA from these genes in a variety of transgene configurations has resulted in scientific advances in three areas. First, a better understanding of milk protein gene expression has enabled the development of helpful guidelines for the construction of efficiently expressed transgenes, including a requirement for regulatory elements within flanking DNA, the presence of introns, processing signals, and translation and protein processing signals. Second, the ability of the mammary gland to exhibit efficient production of heterologous gene products has been tested and the limitations identified. Third, the ability to produce defined, tissue-specific genetic modifications within the mammary gland has allowed researchers to drastically change its development. Such changes could lead to alterations in the physical or chemical properties of manufactured milk, alterations in milk yield or milk composition, alterations in the metabolism and disease resistance of the lactating female, and alterations in the growth and development of the suckling neonate. This review summarizes the current state of transgenic technology as it relates to mammary specific transgenes and illustrates the application of these transgenes to scientific endeavors and to areas of potential commercial interest.