Trangenic Animals - Essay Example

Introduction While animal breeding and the crossing of different breeds of the same species have had a considerable history as long as that of human agriculture, the intermixing of different species has often generated fear or anxiety, if not revulsion. These responses have been captured in the form of the hybrid monster creatures of mythology. The chimera of Greek mythology; part lion, part goat, part dragon, was a creature that was eventually slain by the hero Bellerophon. This had its counterpart in the makara of Hindu myth, with the body of a crocodile and the tail of a fish, also reflected in the Western astrological sign of Capricorn. Chimeras today are no longer mythical nor part of science fiction; modern-day biology through genetic engineering has allowed for the insertion or deletion of part of the genetic code of an animal in order to change that animal's characteristics, or its phenotype. One genetic engineering process that is very much in use today is transgenesis. The gene of animals today can be designed as to mimic specific human genes opening the whole range of possible applications. This paper aims to illustrates how transgenic animals, especially that of mice, is helping in the fight against cancer. It first traces the history of how they came to be and how the concept of an animal model works. Special attention is given to the transgenic mice which has been the most common transgenic animal which is used for medical tests especially that of cancer. Many researchers have been studying the causes and cures of human cancer through the use of transgenic mice. Some of them will be included here to illustrate the use of transgenic mice in helping humans know cancer more deeply. 2. The Development of Transgenesis 2.1 Transgenesis Defined Transgenesis is a radically new technology for altering the characteristics of the animals by directly changing the genetic material. Since DNA contains a universal genetic code for living organisms, it can in principle, be transferred between completely unrelated organisms to produce organisms with useful characteristics that would not be available. Many different genes have now been characterized. This knowledge opens up the possibility of looking for methods of changing genes in ways that are useful. By transferring foreign DNA into animal cells, new genes can be inserted or functioning genes can be switched off. In some cases, new genes can be transmitted to the next generation. The precondition for the elimination or insertion of genes is that is possible to transfer into the cell recombinant DNA that integrates itself firmly into the DNA of the mammal. (EIBE, 1998) 2.2 Techniques for Transgenesis The most direct way of integrating a new gene into a cell is to inject a piece of DNA into the nucleus in the hope that it will become integrated into the genome> This technique is called microinjection. Microinjection is the most frequently used method of inserting a foreign gene into the genome of the mouse in order to develop a model for investigations into hereditary diseases. With each microinjection, 50-500 copies of the modified DNA fragments are inserted into the pre-nucleus. Until recently, pronuclear microinjection of deoxyribonucleic acid (DNA) was the standard method for producing transgenic animals. This technique is now being replaced by more efficient protocols based on somatic nuclear transfer that also permit targeted genetic modifications. Lentiviral vectors and small interfering ribonucleic acid technology are also becoming important tools for transgenesis.(Prosperi, 2000) 3. Transgenic Mice and Cancer 3.1 Underlying Principle What triggers cell to abandon their normal behavior and to divide out of control to produce a tumor Why do cancer cells move to other parts of the body to produce tumor there as well Is the change from a normal cell a consequence of genetic change, external factors, disturbance of the immune system or is cancer only a result of growing old The following questions may be answered by testing known carcinogenic materials into transgenic mice. Transgenic animals come into the picture by being test specimens to know what is responsible for tumor growth and what mechanisms can be employed to counter tumor growth. One such way is to turn off specific genes and determine if it is the one responsible for tumor growth. This way, a better understanding of cancer can be acquired. 3.2 The Development of a Transgenic Mice Model In the laboratory of Philip Leder in Harvard, the transgenic mouse model for the investigation of breast cancer was developed. Two discoveries were of great importance. The first was the identification of a regulating element in the Mouse Mammary Tumor Virus (MMTV) that is active specifically in cells of the mammary glands. Secondly, he and his group identified and cloned oncogenes. The oncogenes myc and ras were analyzed to find out if they lead to breast cancer in mice transformed with these genes. N transgenic mice, examples were found where oncogenes caused cancer in the tissue of the mammary gland. One example was the neu-oncogene. This codes for a protein that serves as a receptor for a growth hormone. In all mice transformed with the MMTV and the xneu-oncogene, cancer broke out usually a short time after puberty. Other oncogenes also caused the development of breast cancer in transgenic mice. Depending on the particular oncogene, the tumors looked different under the microscope. This indicates that each oncogene contributes differently to the development of cancer. 3.3 Other Studies We can now find a plethora of scientific studies concerning cancer with the use of the mouse model. Fleshner and his co-researchers took on the task of developing chemopreventive agents against prostate cancer from conclusive evidence of their efficacy in animal models that emulate human disease. Using male Lady version of the transgenic adenocarcinoma of the mouse prostate mice, They were able to show that we show that administration of antioxidants (vitamin E, selenium, and lycopene) in the diet dramatically inhibits prostate cancer development and increases the disease free survival. (Flesher et.al, 2004) Raghow and his co-researchers also focused on the treatment of prostrate cancer . They evaluated the efficacy of chemopreventive efficacy of toremifene, an antiestrogen, in the transgenic adenocarcinoma of mouse prostate (TRAMP) model Efficacy of treatment was measured by the absence of palpable tumor. What they found was that the substance was indeed efficient in fighting prostrate cancer. (Raghow, 2002) The topic was also the concern of Granziero using transgenic mice as well. (Granziero et. al., 1999) Scientists will be better able to fight Burkitt's lymphoma, a rare but deadly cancer that attacks children and AIDS patients, after Herbert Morse came up with the right genetic mix or what he termed as the "Burkitt's mouse". This new animal model allows researchers to find ways to treat Burkitt's patients who don't respond to the standard treatment. (Morse, 2000) Whey acidic protein SV40 T antigen (WAP-SV-T) hybrid gene was found to be carcinogenic by Tzeng and his co researchers. After injection of the whey acidic protein (WAP)-SV-T hybrid gene into fertilized mouse eggs, eight independent transgenic mouse lines were obtained. Females from three lines developed mammary carcinomas with high frequency, coinciding mostly with lactation. (Tzeng et. al., 1993) Research on the follicular origin of Papilloma or skin cancer was undertaken by Hansen using transgenic mice as clinical models. (Hansen et. al., 1994) 4. Conclusion So far in the discussion, we can see that the use of transgenic mice in cancer research is very prevalent. Its use enables us humans to understand cancer better and come up with solutions. The problem, however, is that many scientists are contesting the appropriateness of relating results from transgenic mice to humans. Many animals are far more genotypically closer to humans. There have been developments lately that humans can be used for clinical tests without wasting lives. Although this remains to be seen, the use of transgenic mouse model can serve as a good source of insights for us humans to understand the malignance that is happening to our body. Sources: EIBE (1998). "Unit 11: Transgenic Animals". EIBE Publications Granziero, Luisa, Stanislaw Krajewski, Peggy Farness, Lunli Yuan, Michele K. Courtney, Michael R. Jackson1, Per A. Peterson and Antonella Vitiello (1999). Adoptive immunotherapy prevents prostate cancer in a transgenic animal model. Eur. J. Immunol. 29: 1127-1138 Hansen, L.A. and Tennant, R.W. (1994) Follicular origin of epidermal papillomas in v- Ha-ras transgenic TG.AC mouse skin. Proc Natl Acad Sci U S A, 91, 7822-6. Morse, Herbert (2000). The development of a Burkitt Mouse Model. Journal of Experimental Medicine 86, 123-135. Prosperi E. (1997) Multiple roles of the proliferating cell nuclear antigen: DNA replication, repair and cell cycle control. Prog Cell Cycle Res 1997;3:193-210. Raghow, Sharan, Massoumeh Z. Hooshdaran, Sanjay Katiyar and Mitchell S. Steiner (2002). Toremifene Prevents Prostate Cancer in the Transgenic Adenocarcinoma of Mouse Prostate Model1. CANCER RESEARCH 62, 1370- 1376 Venkateswaran,Vasundara, Neil E. Fleshner, Linda M. Sugar and Laurence H. Klotz (2004). Antioxidants Block Prostate Cancer in Lady Transgenic Mice. CANCER RESEARCH 64, 5891-5896. Tzeng YJ, Guhl E, Graessmann M and Graessmann A.(1993). Breast cancer formation in transgenic animals induced by the whey acidic protein SV40 T antigen (WAP- SV-T) hybrid gene. Oncogene. Jul; 8(7):1965-71. Read More