Although microinjection is the most common method for DNA delivery, gene targeting may be increasingly used in future. In this approach, embryonic stem (ES) cells in culture arc transfected with a vector which targets the gene to a particular site by homologous recombination.

This technique, though successfully used in mice, has yet to be applied to sheep, where ES cells will have to be isolated first. The first reports of transgenic sheep were published by J.P. Simons (1988) of Edinburgh.

Two transgenic ewes were produced, each. carrying about 10 copies of human anti hemophilic factor IX gene (cDNA) fused with the 10.5 kb BLG gene (BLG = p-lactoglobulin). BLG gene was used, because it is necessary for specific expression of gene in mammary glands.

Consequently, the gene had a tissue specific expression and ewes secreted human factor IX (or alpha-1 antitrypsin) into their milk; this human factor IX is active, even though the expression of transgene is low. The transgenic ewes were born in early summer of 1986 and were successfully mated same year in December.

Four of these animals were female and one male. In one female the protein hα1AT  reached a level of 35 grams per litre of milk. The protein purified from milk had a biological activity indistinguishable from human plasma derived antitrypsin.

The deficiency for hα1AT leads to a lethal disease emphysema, which is a common hereditary disorder among caucasian males of European descent. Therefore any strategy giving high yield of this protein economically will be most welcome. In view of this, transgenic sheep with hα1AT gene will prove very useful as a bioreactor.

Recombinant DNA technique can also be used to increase the ability of sheep for wool growth. For this purpose, genes essential for synthesis of some important amino acids found in keratin proteins of wool, have been cloned and introduced in embryos to produce transgenic sheep.

For instantce, genes (cysE and cysM) for two enzymes (serine acetyltransferase = SAT and O-acetylserine sulphydrylase = OAS), involved in cysteine biosynthesis, were isolated from bacteria and cloned in a vector.