This article provides an overview on transgenic livestock.
Mammary Gland-specific Transgenic Livestock
The modification of milk composition by genetic engineering has been frequently discussed. Milk proteins are made exclusively in the mammary gland and only during lactation.
By using the promoter and regulatory components of a gene encoding a milk protein, it is possible to target the expression of a trans-gene to the mammary gland.
Many groups have been working to take advantage of this natural system to produce important human pharmaceuticals in the milk of dairy animals.
Mastitis is a very important issue for the dairy industry. If left untreated, the presence of bacteria in the udder can lead to changes in the milk and overall health of the animal. Such changes include decreased milk production and increased somatic cell count resulting in subsequent economic losses due to: the dumping of milk; culling and animal replacement costs and increased veterinary and labour charges to treat the infection.
Mastitis is the most costly disease in the dairy industry, with over 1.7 billion dollars a year in losses in the US alone. It is also the most common reason for antibiotic use in dairy cattle and the most frequent cause of antibiotic residues in milk. In addition, current antibiotic treatments are not totally effective and have been implicated in causing antibiotic resistance.
Growth:
Attempts are being made to increase growth and body composition of animals through the transfer of these genes which are responsible for growth-hormone regulation. Experiments with the respective proteo-hormones in growing animals have shown that such effects can be achieved. These gene transfer experiments have been undertaken particularly in pigs and in sheep.
Disease Resistance:
Only a very limited number of genes are known that are able to influence the resistance of domestic animals to diseases. A model for such work is the influenza resistance caused by the Mx-gene.
Quality of Animal Products:
The improvement of the quality or composition of animal products through the transfer of respective gene constructs could provide new prospects for animal production.
Gene Farming:
A suitable combination of tissue-specific promoters and the transfer of these genes into domestic animals may lead to efficient and biologically reliable production of proteins. In particular, efforts have been made to use animals as bioconversion systems.
Transgenic Animal in Pharmaceuticals:
A transgenic animal for pharmaceutical production should:
(i) Produce the desired drug at high levels without endangering its own health and
(ii) Pass its ability to produce the drug at high levels to its offspring.
The current strategy to achieve these objectives is to couple the DNA gene for the protein drug with a DNA signal directing production in the mammary gland. The new gene, while present in every cell of the animal, functions only in the mammary gland so the protein drug is made only in the milk.
Since the mammary gland and milk are essentially “outside” the main life support systems of the animal, there is virtually no danger of disease or harm to the animal in making the “foreign” protein drug. Because of the long time periods involved and low success rates, developing transgenic animals is currently very expensive, as the dollar amounts in Table 18.2 indicate.
Although most protein drugs are made in milk (Table 18.3), a notable exception is human haemoglobin that is made in Swine blood to provide a blood substitute for human transfusion. Because haemoglobin is naturally a blood protein, it is likely to be one of few exceptions to the usual method of production in milk. Furthermore, the economics of blood production are less favorable, because to recover human haemoglobin, the animal producing it must be slaughtered.
