Transgenic animals and their importance in experimental medicine

Today, thanks to gene transfer methods, animals that carry the genes of a foreign species in their genomes and exhibit these characteristics in their phenotype; They are called “transgenic organisms”. We can also see these genetically modified animals as “biofactories”.

Recombinant protein production, establishment of disease models, development of high yielding breeds and xenotransplantation studies are among the main production reasons of transgenic animals. In the 1980s, gene transfer studies were carried out in a range of species from goats to pigs and even fish, especially mice, whose genetics have been known for many years.

Gene transfer can be done by various methods, such as DNA microinjection, electroporation, transfer via gamete cells and embryonic stem cell injection. These applications are costly, very difficult, and require a great deal of effort. There is no other way to catch up with developed countries in the field of biotechnology and to maintain scientific competition.

Another critical step regarding transgenic animals is bioethics. Apart from the ethical permissions and regulations required for Animal Experiments and practices, there are rules and regulations to be followed from the care and breeding of transgenic animals to the disposal of their medical waste.

Barrier systems and special protected areas are required for the housing, production and maintenance of these non-nature species without causing any contamination. Various working groups in European countries have formed various societies in order not to produce the same transgenic animals and to enable teams working on gene transfer in different countries to communicate with each other (International Society for Transgenic Technologies). Again, various organizations have web sites (Mouse genome informatics) to find the right disease model animals on the internet. Documents called GA passports are prepared for these animals and it is obligatory to give information about all vital, production and models of the animal. The ethics and current problems of these issues are discussed in many international scientific meetings (SALAAM and TTMeetings).

Usage areas and importance in medicine

In addition to the use of transgenic animals in many areas from increasing animal production to interspecies organ transfer, from recombinant protein production to pet fish, their scientific importance is gradually increasing because they allow understanding the molecular mechanisms of diseases and the functions of genes for medical research purposes, with the creation of human disease models in animals. Among transgenic animals, mice are the most commonly used species as 90% of their genomes are known. As examples of human disease models; Ankylosing spondylitis (AS) an autoimmune disease and arthritis model HLA-B27 transgenic mouse, P53 gene silenced on chromosome 17 by gene targeting technology, Li-Fraumeni syndrome model P53 knockout mouse can be given.

Today, it has been possible to silence up to 10,000 of the 20,000 genes in the mouse genome and to develop 500 different knockout mouse models. Among the gene editing technologies developed in recent years to improve classical gene targeting methods, the CRISPR-Cas9 system stands out as the fastest, cheapest and most reliable system.

Transgenic and knockout mice; Alzheimer’s, cancer, obesity, hypertension, cardiovascular and neurodegenerative diseases, cystic fibrosis, huntington’s disease and Parkinson etc. It is used in the elucidation and modeling of the complex molecular mechanisms of diseases and in gene therapy research.

Another reason for the use of transgenic animals in medicine; It is the production of desired proteins, primarily from milk, from these animals. Many molecules such as coagulation factors, fibrinogen, antithrombin 3, hemoglobin, serum albumin, lactoferrin, lysozyme have been produced and sold commercially.

In recent years, these developments in the field of biotechnology; It is clear that people have important responsibilities within the framework of ethical principles and values ​​in terms of taking the necessary biosecurity measures, as well as in the use of transgenic applications and products derived from them.

The situation in Turkey

Producing Turkey’s first clone creatures, Oyalı and Zarife, in 2007, Istanbul University Faculty of Veterinary Faculty Member Prof. Dr. The team, led by Sema Birler, carried out a joint study with the researchers of the University of Hawaii in 2013 and succeeded in producing the first transgenic rabbits and lambs of our country. Gene transfer was provided for transgenic rabbits produced in 2013 through a TÜBİTAK supported COST project using both intracytoplasmic and pronuclear injection methods, and green fluorescent images were obtained in the born offspring.

In the first transgenic sheep study called Çimen, Prof. Dr. Hyperactive plasmid (piggyBac transposase-based, self-inactivating, single-construct plasmids containing both transposase and transposon, pmGENIE-3) developed by Stefan Moisyadi was transferred to sheep embryos in vitro by intracytoplasmic gene injection (ICSI) method. The production of the first transgenic rabbits and lambs skipped an important step in scientific studies for the production of valuable drugs from transgenic animal milk.

“Pharmaceutical Production with Transgenic Technology” in the “Vision 2023” National Science and Technology Policies 2003-2023 Strategy Document, which was determined among the 2007-2013 targets of our country and prepared by TUBITAK, and the Report of the Ninth Development Plan of the TR Prime Ministry State Planning Organization, Pharmaceutical Industry Specialization Commission. identified as a strategic goal.

In recent years, many centers and research institutions working with transgenic animals have been opened and started to operate in our country.

Laboratory Animal Science Department, which was established in 1994 within the Aziz Sancar Experimental Medicine Research Institute; As one of the leading departments of its field in our country, it successfully carries out its education and training activities. The Department also maintains collaborations with national and international scientific organizations in order to further improve the services it offers to research projects.

Department of Laboratory Animal Science, operating under Aziz Sancar Experimental Medicine Research Institute; With the recent obtaining of the Transgenic Animal Research License and the opening of the use laboratory, it aims to provide researchers with the opportunity to produce projects with high international acceptance and to create a good working archive by preserving the tissues and embryos of these creatures.

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