Give examples of the use of transgenic animals for the production of useful products
Gene transfer in farm animals can be used to improve the productivity and quality of livestock products, increase resistance to diseases and create transgenic animals - bioreactors of valuable biologically active substances. Ernst LK (1996) reports that in transgenic pigs with the growth hormone gene, the final live weight was 15.7% higher than in control animals. According to Brem G. et al. (1991), offspring of transgenic pigs receiving the corresponding modified diet with an increased protein content and an additional amount of lysine showed higher average daily weight gain. In contrast to these results, cases of espression of transgenes without a phenotypic effect are not uncommon. This was clarified already in the first paper (REHammer et al., 1985) - in the transfer of the human growth hormone gene, when transgenic rabbits, swine and sheep were obtained, but no phenotypic changes were observed in any case of expression of human growth hormone in animals. V. G. Pursel et al. (1987) with the same gene, piglets with established expression of this gene were obtained, but also without changing the growth rate. These same researchers (1988, 1989) also did not register the corresponding growth acceleration in transgenic pigs with the growth hormone gene. Transgenic sheep with the growth hormone gene had an elevated level, but did not differ from the control ones by the growth rate. However, transgenic pigs had a more than twofold decrease in the thickness of the fat, while in transgenic sheep the fat content was approximately 4-5 times lower than in the control analogs. In this regard, a number of suggestions were made, one of which relates the absence of a specific phenotypic effect in animals with weak recognition by its receptors of foreign hormone molecules or with post-translational modifications (K.A. Ward, C.D. Nancarrow, 1991). This assumption soon gets experimental evidence on actively growing pigs, with additional copies of the gene of its own growth hormone (V.D. Vize et al., 1988) built into the genome. However, subsequent experiments on sheep gave a different result. Hopes that the sheep's own gene will "work" better in the sheep's body than the alien gene did not materialize. Transgenic sheep with a high content of sheep growth hormone showed a slight increase in body weight and were physiologically abnormal.
The difference in growth rate between transgenic mice and transgenic agricultural animals.animals, some researchers explain as follows. Most of the pigs used in the gene transfer experiments originated from populations in which breeding for long-term productivity was conducted, while the selection for this indicator was not carried out in the mice line. Indeed, mice, in the population of which the selection for growth rate was carried out for 30 generations, had a slightly smaller live mass in comparison with transgenic peers. Therefore, the introduction of a foreign gene into a population of lines of mice not subjected to breeding for growth rate causes a jump to a higher growth level. Genetic growth potential in pig populations, on the contrary, is not far from the potential plateau, and therefore additional administration of growth hormone or transfer of its gene does not have a significant effect in growth rate. Another explanation for the lack of growth acceleration of transgenic animals is associated with the need to increase not only growth hormone, but also some other, not yet known growth stimulants.
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Unregulated expression of the growth hormone gene, both autologous and heterologous, can lead to a decrease in the life span of transgenic animals due to pathological metabolic disorders, the development of acromegaly (excessive overgrowth of individual parts of the face, extremities and internal organs) and exposure to various infectious diseases. For example, transgenic sheep with a high content of bovine growth hormone in the blood developed diabetes mellitus - a typical symptom of acromegaly (SE Rexroad et al., 1990). In another study, diabetes mellitus was noted in transgenic sheep that actively express their own growth hormone. Animals died during the first year of postnatal life (C.D. Nancarraw et al., 1991; K.A. Ward et al., 1989). Transgenic pigs with hypersecretion of the hormone were less in live weight at birth than littered offspring, more sluggish, with an oppressed appetite, a tendency to arthritis, and most of them also did not live more than a year (V.G.Pursel et al., 1987, 1989). It became obvious that the constantly high level of production of growth hormone in animals is not a positive factor in their productivity. An analysis of these experiments suggests that the use of transgenic technology to alter the growth and composition of the tissues of domestic animals requires a deeper understanding of the processes of genetic growth regulation. According to LK Ernst and co-workers. (1993), the directed effect on one hormone of the complex hormone-growth cascade will not be effective until complex gene constructs with fine regulation of metabolic processes are created.
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The creation of transgenic animals opens real prospects for improving the quality or composition of livestock products. For example, it has become possible to reduce lactose in milk by creating transgenic cows and sheep that have a mammary-specific promoter (a region of DNA with which RNA polymerase binds to begin mRNA synthesis) linked to the lactose gene. In this case, in the milk of cows (sheep) lactose can be split into glucose and galactose. Such milk could be used in feeding newborn children suffering from hereditary intolerance to lactose. To such children in infancy, milk should be given only after its treatment with enzyme preparations. In addition, milk could be useful for various gastrointestinal diseases of a person, accompanied by a decrease in the activity of lactase (beta-galactosidase). The presence in the milk of a diverse microflora creates problems related to storage, processing, consumption of milk and animal health. In this connection, genes responsible for the production of antibodies against certain pathogenic microorganisms are constructed (R.D.Bremel et al., 1989; U.H. Weidle et al., 1991). An important task is to obtain milk and dairy products containing a thermostable enzyme lysozyme of microbial origin. When milk is pasteurized, this enzyme, which has a pronounced antibacterial property, will not lose its activity, which will significantly increase the shelf life of milk and products obtained from it. In the acidic environment of the gastrointestinal tract, lysozyme is inactivated. The possibility of introducing genes encoding antibodies with protective properties against pathogenic microbes - causative agents of mastitis of cows is considered.
The genetic construct pGoatcasGMCSF was created by the Institute of Cytology and Genetics of the SB RAS (Novosibirsk) and the Institute of Molecular Genetics of the Russian Academy of Sciences (Moscow). It contained the regulatory region of the goat's alpha-S1-casein gene, which carries the granulocyte-macrophage gene of the colony-stimulating factor (GM-CSF ) of a person (IA Serova et al., 2011). In experiments on the injection of this recombinant DNA into zygotic pronuclei, 4 transgenic mice were obtained. The PCR method shows the tissue specificity of human GM-CSF expression only in the mammary gland of lactating females. Since this construction is tissue-specific, it is regulated by the physiological signals of pregnancy and lactation.
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The achievements of genetic engineering can be used in changing the quality and yield of sheep's wool. Further improvement of the sheep's wool characteristics to a certain extent depends on the degree of supply of hair follicles with nutrients necessary for their active functioning. The main obstacle physiologists consider the restriction of the energy reserve to ensure the processes of cell proliferation and amino acids (lysine, methionine, arginine, histidine and cysteine) for the synthesis of keratin fibrin wool. Enzymatic processes caused by the microflora of the rumen do not always fully ensure the synthesis of the necessary amino acids, since during the splitting of the protein of the feed, most of them go to the synthesis of microorganisms of their own proteins, which reduces the level of amino acids important for the growth of wool. Therefore, the priority task of recombinant DNA technology, aimed at improving the characteristics of sheep's wool, is to increase the efficiency of sheep feeding.
In order to increase the amount of sulfur-containing amino acids (eg cysteine) required for the biosynthesis of keratin proteins of sheep's wool, Rogers G.E. (1990) considers it expedient to create transgenic sheep having bacterial genes encoding the synthesis of cysteine in their genome. These genes should be expressed only in the epithelium of the gastrointestinal tract of the sheep and cause the use of sulfur formed as a result of the enzymatic processes of microorganisms. He obtained the first transgenic lamb containing genes of serine acetyltransferase (SAT) and O-acetylserinesulfhydrylase (OAS) from Salmonella typhimurium in its genome. K. A. Ward et al. (1990) used SAT and OAS of Escherichia coli, linked to a gene construct consisting of a sheep metallothionein-1a promoter, which causes zinc-dependent expression. Research in this direction continues.
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