Transgenic Animals: Methods Of Production, Examples & Applications

What are Transgenic Animals?

Transgenic means that one or more DNA sequences from another species have been introduced by artificial means. Animals usually are made transgenic by having a small sequence of foreign DNA injected into a fertilized egg or developing embryo.

Transgenic animals are animals which have been genetically transformed by splicing and inserting foreign animal or human genes into their chromosomes. Transgenic animals with changes in the germ line are heritable from generation to generation within the herd, and this heritability has potential to facilitate long-term productivity gains. Transgenic animals are animals that are genetically altered to have traits that mimic symptoms of specific human pathologies. They provide genetic models of various human diseases which are important in understanding disease and developing new targets.

The first transgenic animal was produced in 1983 when genes for human growth hormone were introduced into mice.Transgenic animals such as mice, rat, rabbit, pig, cow, goat, sheep and fish have been produced. The various steps involved in the production of transgenic organisms are:

  • Identification and separation of desired gene.
  • Selection of a vector (generally a virus) or direct transmission.
  • Combining the desired gene with the vector.
  • Introduction of transferred vector into cells, tissues, embryo or mature individual.
  • Demonstration of integration and expression of foreign gene in transgenic tissue or animals.

Methods for Creating Transgenic Animals

The following are recent animal gene transfer techniques used in the production of transgenic animal production:

Microinjection Method

DNA microinjection method is accomplished by the transfer of a desired gene construct from another member of the same species or from a different species into the pronucleus of a fertilized ovum, which is subsequently implanted into the oviduct of recipient animals. This results in the recipient animal giving birth to genetically modified offspring.

This method has many advantages like, exogenous genes are expressed in an efficient manner, the size of the inserted DNA molecule has no clear limit and moreover this technique is simple, inexpensive and can be applied to a wide variety of species. However, this technique cannot be used into the cell at later development stage, the injected transgene may cause a change in the normal physiological processes of the animal, time consuming and requires extensive intellectual, financial and material assets and the success rate of producing transgenic animals by these methods is very low.

Somatic Cell Nuclear Transfer (SCNT)

This is a technique in which the nucleus (DNA) of a somatic cell is transferred into an enucleated metaphase-II oocyte for the generation of a new individual, genetically identical to the somatic cell donor. Somatic cell transfer may be used to generate multiple copies of genetically elite farm animals, to produce transgenic animals for pharmaceutical protein production or xeno-transplantation or to preserve endangered species.

Retrovirus-mediated Gene Transfer

Retro virus-mediated gene transfer method is is mediated by means of a carrier or vector; generally a virus or a plasmid. Retroviruses are commonly used as vectors to transfer genetic material into the cell because of their ability to infect host cells .A retrovirus is a virus that carries its genetic material in the form of RNA rather than DNA. The code in the viral RNA is reverse transcribed to produce DNA, which is then incorporated into the host cell.

The most important features of retrovirus as vectors are the practically ease and effectiveness of gene transfer and target cells specificity. Retrovirus mediated gene transfer is a powerful tool that can be used to understand gene functions. This method is advantageous because this system is technically simple, readily integrates and passes through the germ lines allowing for their propagation into subsequent generations and causes minimal disruption to host DNA.

Embryonic Stem (ES) Cells Mediated Gene Transfer

This method is based on the principle that, the presence of transgenes can be tested at the embryonic state. ES cells are pluripotent cells, found in the inner cell mass (ICM) of embryos at the blastocyst stage of development which not yet differentiated and maintain the ability to develop into any type of tissue during the embryonic and foetal development. DNA can be introduced into the ES cells in vitro.

The desired DNA containing embryonic stem cells grown at blastocyst stage, are incorporated into the host’s embryo and then embryo inserted in the uterus of a surrogate mother, resulting in a chimeric animal. The method uses homologous recombination of DNA to permit precise targeting of DNA in embryonic stem cells. If the homologous sequence to be introduced into the cell carries a mutation or a gene from another species, the new sequence will replace the specific targeted gene. This is the method of choice for gene inactivation therefore called as “knock-out” method, mainly used in the study of the genetic control of developmental processes.

Application Of Transgenesis

  • Transgenesis is a powerful tool to study gene expression and developmental processes in higher organisms.
  • Transgenesis helps in the improvement of genetic characters in animals.Transgenic animals serve as good models for understanding human diseases which help in the investigation of new treatments for diseases.Transgenic models exist for many human diseases such as cancer, Alzheimer’s, cystic fibrosis, rheumatoid arthritis and sickle cell anemia.
  • Transgenic animals are used to produce proteins which are important for medical and pharmaceutical applications.
  • Transgenic animals are used for testing toxicity in animals that carry genes which make them sensitive to toxic substances than non-transgenic animals exposed to toxic substances and their effects are studied.
  • Transgenesis is important for improving the quality and quantity of milk, meat, eggs and wool production in addition to testing drug resistance.
  • Transgenic mice are used in toxicity and in testing the safety of vaccines.
  • Transgenic swine are used to produce human haemoglobin.

Examples of Transgenic Animals

  • Transgenic Fish
  • Transgenic Cattle/Cow
  • Transgenic Pig
  • Transgenic Mice
  • Transgenic Sheep