Tell us about the achievements of genetic engineering in breeding animals that are resistant to various diseases



 

Increasingly important is the selection of animals for resistance to disease. Unlike vaccination, the effect of which is manifested during the life of specific individuals, genetic engineering immunity can have a hereditary character, which will allow the production of agricultural products. animals resistant to certain infectious diseases. Resistance to a number of diseases is a polygenic sign. For example, resistance to trypanosomiasis of certain African breeds of cattle is observed against the background of their frying and undemanding conditions of feeding and maintenance. However, the resistance of the body can be based on individual genes. Examples include resistance to diarrhea in newborn piglets or resistance to influenza in mice. This served as the basis for obtaining animals with transgens, which, perhaps, will create immunity to certain infectious diseases. In this area of ​​genetic engineering, research on the specific antiviral effect of the genes of monoclonal antibodies is at the forefront. The mechanism of action of the latter should be to a certain extent similar to the specific antiviral immunization of animals. Transgenic mice that produce antibodies against specific antigens without prior immunization or exposure to infection have been obtained (Storb U., 1987). The light and heavy chain genes of monoclonal antibodies against 4-hydroxy-3-nitrophenylacetate were integrated into the genome of rabbits and pigs (U. Weidle et al., 1991). The titer of specific antibodies in the serum of transgenic animals was found to be 100 and 1000 μg / ml, respectively. There have been reports of the production of transgenic mice, sheep and pigs with gene constructs encoding the alpha and chi chains of antibodies against phosphorylcholine (D.Lo et al., 1991). The authors observed a high level of mouse IgA, but only in transgenic mice and pigs. G. Brem et al., Since 1991, isolated and cloned the mouse gene Mx, responsible for immunity to the influenza A virus, and are working to produce transgenic pigs based on the use of this gene. The possibility of obtaining transgenic animals with an increased concentration of lactoferin in the tissues of the mammary gland is investigated with the aim of increasing resistance to mastitis. Work is also underway to obtain animals that have an antisense RNA transgene in their genome. Expression of the latter in cells leads to hybridization with the sense RNA, as a result of which the replication of the viral gene is suppressed. Thus, Russian scientists (TI Tikhonenko, MI Prokofiev, LK Ernst, 1991) constructed the gene of antisense RNA against adenovirus and produced transgenic rabbits. Cell lines of animals (cell culture from kidneys) having a transgene showed high resistance to adenovirus compared to control cell lines. The same researchers demonstrated the stability of animals with a transgene of antisense RNA against bovine leukemia at the organism level to infection with the virus-causative agent of this disease. Thus, in transgenic rabbits with the mentioned gene, the antibody titer against p24 antigen was significantly lower (1: 500) than in control animals (1: 8000). The possibility of creating intracellular immunization against certain viruses is shown. Transgenic chickens were obtained, the cells of which expressed the capsid protein of the leukemia virus, which contributed to their resistance to this disease.

It is known about the existence of breeds with hereditary resistance to bacterial infectious diseases - mastitis (cows), dysentery (newborn piglets), cholera (poultry). If one gene is the basis of resistance to each of these diseases, you can try to create transgenic animals that carry it. Currently, vaccines and medications are used to control infectious diseases of domestic animals. Ill animals are isolated, and careful observation is carried out for the healthy. The cost of all these activities can reach 20% of the total cost of the final product.

To deduce lines of animals that are resistant to infectious agents, another approach can be used, consisting in the creation by transgenesis of inherited immunological mechanisms. From this point of view, consider the most diverse genes responsible for the immune system: genes of the main histocompatibility complex, T-cell receptors, lymphokines. The most encouraging to date are the preliminary results obtained when mice, rabbits and pigs are introduced genes encoding the H and L chains of any monoclonal antibody. The idea of ​​this approach is to provide the transgenic animal with an inherited defense mechanism that allows for immunization with vaccines.

The introduction into the recipient organism of antibody genes that bind to specific antigens has been called in vivo immunization. To this end, the H and L chains of the immunoglobulins of the monoclonal mouse antibody to the antibody bound to 4-hydroxy-3-nitrophenylacetate were injected by microinjection into the fertilized mouse, rabbit and porcine egg cells. In all cases in the serum of transgenic animals, the corresponding activity of the monoclonal antibody was detected. However, the number of monoclonal antibodies containing H- and L- chains was small. To establish whether this problem can be solved, it is necessary to test various transgenic constructs.

The possibility of including in the cells of the organism genes responsible for the synthesis of proteins that are of great importance in medicine and veterinary medicine, has created the basis for the strategy of using transgenic animals as bioreactors. Most of these proteins are still isolated from human tissues and biological fluids. For example, clotting factor, interferon, alpha-1-antitrypsin and other proteins are obtained from blood, growth hormone from the pituitary. They are produced in small quantities because of the high cost and difficulty in isolating human tissues. In addition, they can be infected with pathogenic microorganisms, such as pathogens of hepatitis, AIDS, etc.

 


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