TRANGENIC ANIMALS

Transgenic animals are those animals whose genetic makeup has been altered by the insertion or deletion of genes under specific conditions. These genetically modified organisms are widely used in the field of biology, healthcare, scientific research, agriculture and pharmaceutical industry etc. New and advanced technologies are used to produce new recombinant genes and these methods have many advantages but at the same time, they have certain drawbacks as well. With that, transgenic animals have their DNA altered in such a way that they contain foreign DNA incorporated in them which is unnaturally introduced in their genome.

The bacteria Escherichia coli was the first organism whose genome was manipulated through artificial means. This led to significant advances in genome modification technology and ultimately led to the production of transgenic animals. The first such transgenic animals were mice. Genome modification of mice led to the interpretation and techniques of genetic engineering in many other animals like sheep, cows, goats, etc. The main idea of animal transgenesis was to generate pharmaceutical products and produce other products for the welfare of mankind.

There are many techniques and methods which are used nowadays to produce transgenic animals. One of the most common techniques is the use of retrovirus. Retrovirus can cause different diseases in mammals like immunodeficiency syndrome, herpes, etc. It is basically an RNA virus because after crossing the cell membrane barrier, the viral RNA transforms into DNA hence it can alter the genome of the host cell. Therefore, it can be used effectively as a host-specific transfer agent especially in germ-line transmission. But it has some drawbacks as well: Firstly, it is not able to recognize specific target cells, it is host-specific, and it also requires dividing cells for its integrations.  Secondly, sperm mediated DNA transfer is also very helpful in producing transgenic animals, for example in vitro fertilization of rabbits. But in this technique genes are not always expressed; therefore it has certain limitations to perform well when incorporated into the host genome.  Thirdly, transgenic animals are also produced by Embryonic stem cells. They can produce organisms with two distinct cell lines and amongst those two, one contains the demanded genome. The first genetically modified organisms through this technique were mice.  Embryonic stem cells can produce many different types of cells. This method is applicable in all animals which can alter their embryonic stem cells. This method is the most widely used method because of its certain advantages; we can control the site where transgenic integration is going to take place by the existing genes which help us to study human genes. Moreover, the homologous DNA recombination technique can be used to easily target embryonic stem cells.  Lastly, the pronuclear injection technique is also used to introduce foreign genes in animals. In this technique, the gene of interest is injected into the zygote of the target organism directly. The first genetically modified livestock species like sheep, rabbit, etc. were produced through this very technique but there are some major drawbacks of this technique as well; the transgenic animals produced through this technique do not have a stable genome that was integrated from the host. Secondly, the cells of such transgenic animals may or may not contain the required gene. Thirdly, the site of transgene integration is unpredictable in the host genome through this technique which results in drastic variations in the results. Lastly, the most effective method of incorporation of foreign genes is called nuclear transfer.  In this technique, somatic cells from the mammary glands are used to produce transgenic animals. One such genetically modified organism was a sheep named Dolly. After the incorporation of the gene, chemical and mechanical methods are used to stimulate the activation of the zygote. This process is also called cloning and it can generate a series of individuals having the same genetic makeup from a single DNA.

Transgenic animals have various applications in the field of biotechnology. Transgenic animals are used in agricultural techniques. They enhance the metabolism, produce diverse agricultural products, increase the disease resistance of crops, produce crops that are resistant to pests, etc. And this eventually leads to the enhancement of the life of human beings. Moreover, pharmaceutical products are made by transgenic animals, such animals are called Transpharmers. When human genes are inserted in such animals, they are capable of producing proteins specific to human beings. The products of such transgenesis are ATIII antitrypsin and Tpa. Furthermore, high-value pharmaceutical products are produced which is one of the most effective outcomes of animal transgenesis. We can produce pharmaceutical products in various biological fluids like blood, seminal fluids, and saliva. There are many advantages of using urine-based systems; they can be expressed in both sexes, they can be collected soon after birth, and there is low content of contaminated protein in the urine. But this system is a time-consuming process and is not cost-effective. Therefore, milk is the most preferred vector for gene expression because it can give the desired results and significant volumes of product. With that, the transgenesis of livestock can produce quality meat, it can enhance milk production, good quality of wool, resistance to disease and it is profitable as well due to enhanced production of desired products. Low-lactose milk is also produced using transgenic animals, lactase enzyme is used in the production of low-lactose milk which is economically profitable. This is achieved by using alpha-lactalbumin, which allowed the mice to be able to produce milk with 20% less lactose content. Another goal of biotechnology is to increase milk production in animals, they do so by limiting the lactation period. Increased alpha-lactalbumin genes introduced in swine are helpful for increased milk production. These modified milk properties are not just important as dairy products, but these humanized bovine and goat milk can be beneficial for human health as well. One of its major examples is the expression of human lactoferrin in milk, which demonstrates antibacterial, antifungal, and antiviral properties which are beneficial for human health. Furthermore, human lactoferrin can initiate the increased growth of microbiota residing in the human intestine of breastfeeding infants., it can also keep the intestine healthy by promoting intestinal growth in vitro and it provides promising results for the innate immune system of infants. Transgenesis in livestock is also the major step towards the production of good quality carcasses and improved meat production. The first such animal transgenesis performed on mice showed improved growth and body weight whereas, when this same technique was applied on pigs, they showed only a slight increase in growth, yet they had increased renal diseases, gastric ulcers, etc. Moreover, such transgenic pigs are also produced which are capable of digesting dietary phosphorous by increased production of salivary phytase. This helps in decreasing phosphorous pollution which is significant for reducing environmental pollution.

Lastly, another research outcome with positive results in the field of animal transgenesis is the study of aging. When the replication of DNA occurs by a series of mitosis, the size of telomeres (highly repetitive DNA sequences) is altered. This alteration and hence shortening in the size of telomeres lead to the limited ability of cells to regenerate and this eventually results in aging. In the rabbit, human telomerase reverse transcriptase which is able to enhance the regeneration of telomere was incorporated by adenovirus which was able to produce ischemic wound healing in an old rabbit and no diverse immune response was seen in such rabbits, hence this technique has important application in the field of gene therapy.

By: Rutba Khan

References

Animal Transgenesis Technology: A Review. (n.d.). Retrieved December 8, 2021, from https://www.tandfonline.com/doi/pdf/10.1080/23311932.2019.1686802.

authors, A., Amare Bihon Asfaw  & Ayalew Assefa  |, Additional informationFundingThe authors received no direct funding for this research.Notes on contributorsAmare Bihon AsfawAmare Bihon Asfaw is an Assistant Professor of Veterinary Reproduction and Obstetrics (VROB) at the Department of Clinical Medicine, & Acquaah. (n.d.). Animal Transgenesis Technology: A Review. Taylor & Francis. Retrieved December 8, 2021, from https://www.tandfonline.com/doi/full/10.1080/23311932.2019.1686802.