Molecular Biotechnology: Principles and Applications - Glick, B., Pasternak, J. 2002

Molecular Biotechnology of Microbiological Systems
Transgenic Animals

To breed improved varieties of domestic livestock and poultry (such as cows with higher milk yields, sheep with superior wool quality, or hens with increased egg production), numerous rounds of crossbreeding and Selection are carried out, each time using animals with the best characteristics as breeding stock. As a result, more or less pure lines of highly productive animal breeds can eventually be obtained. Although time-consuming and costly, this breeding and selection strategy has proven exceptionally successful, and today almost all aspects of the biological foundations for developing new livestock breeds can be traced back to it. However, once an effective genetic line has been established, introducing new traits via traditional crossbreeding and selection becomes increasingly difficult. For instance, a line carrying a new "valuable" Gene may also harbor "harmful" genes, rendering the offspring less productive. Therefore, to ensure that a new, improved line retains its original beneficial traits while acquiring novel ones, an entirely new strategy must be developed.

Successful experiments involving the Introduction of foreign genes into mammalian Cells, coupled with the potential to create genetically identical animals via nuclear transfer—transplanting an embryonic Cell Nucleus into an enucleated oocyte (nuclear transfer, or cloning)—have made it possible to incorporate individual functional genes or entire gene clusters into the chromosomal DNA of higher animals. The strategy employed is as follows.

✵ The cloned gene is injected into The Nucleus of a fertilized egg.

✵ The microinjected fertilized eggs are implanted into a female recipient (as Cytology/cytology/19.html">Mammalian Embryonic Development cannot successfully proceed under any other conditions).

✵ Offspring that have developed from the implanted eggs and contain the cloned gene in all their cells are selected.

✵ Animals carrying the cloned gene in their germline cells are crossbred to establish a new genetic line.

This approach has numerous Structure/179.html">Practical Applications. For example, if the product of the introduced gene stimulates growth, Transgenic Animals will grow faster on less feed. Improving feed conversion efficiency by just a few percentage points can significantly reduce the cost of the final product (beef, pork, etc.).

METABOLISM/2.html">THE CONCEPT OF genetically modifying animals by introducing genes into fertilized eggs was successfully realized in the 1980s. As in many emerging scientific fields, A number of new terms were introduced to facilitate communication among researchers. Thus, an animal whose genotype has been altered by introducing foreign (exogenous) DNA was termed transgenic, the introduced DNA a transgene, and the entire process transgenic technology, or transgenesis. Although Experiments on the genetic modification of Multicellular Organisms via transgene delivery are time-consuming, transgenesis has nonetheless become a powerful tool for investigating the Molecular Basis of mammalian Gene Expression and development, for creating model systems to study human diseases, and for genetically modifying the mammary gland cells of animals to produce medically important Proteins in their milk. The term "pharming" was even coined to describe The process of obtaining authentic human proteins or Pharmaceuticals from the milk of transgenic livestock ("pharm animals"). Milk is an ideal medium because it is produced in large quantities by the animal and can be harvested as needed without harming the creature. The novel protein expressed by the mammary gland and secreted into the milk must not exert any adverse side effects on the normal physiological processes of the transgenic animal, and its post-translational modifications should closely resemble those occurring in human cells. Furthermore, isolating the protein from milk—which contains various other proteins (Table 19.1)—should be straightforward.

Class="center">Table 19.1. Protein composition (g/L) of cow and sheep milk