Production of proteins in the milk of transgenic livestock: problems, solutions, and successes.

The milk of livestock can be modified dramatically by introducing foreign DNA into the germline. Exclusive expression of this DNA is ensured by the presence of regulatory sequences from mammary gland-specific genes. In sheep > 50% of the protein in milk can be encoded by a transgene and it appears that the foreign protein is additional to the normal complement of proteins. However, many technical hurdles (DNA configuration, low efficiency of transgenesis, and transgene stability) still prevent the routine use of this technology. In addition, such milk products have not yet received regulatory approval. These difficulties are not insurmountable. Transgenic methods can also be used to study the molecular basis of milk biogenesis. The effect on milk production in mice with all endogenous alpha-lactalbumin genes removed and in mice in which the murine genes were then replaced with human homologues is described. alpha-Lactalbumin, and consequently lactose, is essential for normal milk formation, and the human gene is expressed more efficiently than the murine gene.