Transgenic Animals

Transgenic Animals

Definition:
Transgenic animals are organisms with a foreign gene (called a transgene) introduced into their genome, modifying their DNA. These animals are also referred to as genetically modified organisms (GMOs).

Applications of Transgenic Animals

1. Production of Human Proteins:

• Used to produce therapeutic proteins like:

• Insulin

• Growth hormones

• Human lactoferrin

2. Drug Production:

• Serve as bioreactors for the production of pharmaceutical drugs.

3. Vaccine Development:

• Transgenic animals can produce monoclonal antibodies utilized in creating vaccines.

4. Improvement in Milk Yield:

• Applied in cattle breeding to increase milk production.

5. Enhancing Growth and Survival:

• Modifications improve growth rates and enhance the survival of offspring.

Historical Milestones in Transgenic Animal Research

• 1891:

• Walter Heape successfully transferred embryos in Angora rabbits for the first time.

• 1974:

• Rudolph Jaenisch and Beatrice Mintz reported the first genetic modification in animals.

• 1980:

• Dr. Frank Ruddle and Gordon created the first "transgenic animal" (mouse) by inserting foreign genes into its genome.

Significance

• Transgenic animals represent a revolutionary advancement in biotechnology, offering solutions for medicine, agriculture, and basic scientific research.

Techniques to Produce Transgenic Animals

1. Pronuclear Microinjection

• Description:

• A widely used early technique for producing transgenic animals.

• Involves injecting foreign DNA directly into the pronucleus of a fertilized oocyte.

• The oocyte then develops into an organism that carries the transgene in its genome.

• Applications:

• Initially developed for mice and later adapted for livestock (e.g., cattle, pigs, and sheep).

• Efficiency:

• Success rates for transgene integration:

• ~3% for small animals like mice, rats, and rabbits.

• ~1% for livestock such as cattle, pigs, and sheep.

• Limitations:

• Low Efficiency: Transgene integration occurs in a small fraction of embryos.

• Mosaicism:

• Animals may develop with some cells containing the transgene and others without it.

• This leads to inconsistent expression of the desired trait

2. Stem Cells

Use in Transgenic Animal Production

• Embryonic Stem (ES) Cells:

• Extensively used to create transgenic mice.

• Isolated from the inner cell mass of a blastocyst (an early-stage embryo).

• Characteristics of ES Cells:

• Pluripotent:

• Can differentiate into almost any tissue type in the body.

• Immortal-like Potential:

• When cultured under optimal conditions, ES cells can divide indefinitely.

• This makes them ideal for DNA manipulation and transgene insertion.

• Process of Creating Transgenic Animals with ES Cells:

• Transgenic ES cells are created by inserting foreign DNA into their genome.

• These transgenic ES cells are then introduced into a developing mouse embryo.

• The transgenic cells integrate into the embryo and multiply, contributing to the formation of various tissues.

• Applications:

• Widely used in genetic research for:

• Studying gene function.

• Modeling human diseases.

• Developing new therapeutic approaches.

3. Somatic Cell Nuclear Transfer (SCNT)

Overview

• Definition:

1. A laboratory technique used to create a viable embryo using a somatic cell nucleus (from a body cell) and a denucleated egg cell (an egg cell without its nucleus).

• Process:

1. Denucleation:

• The nucleus is removed from an egg cell (oocyte).

2. Nuclear Transfer:

• The nucleus from a donor somatic cell is inserted into the denucleated egg cell.

3. Activation:

• The reconstructed egg is stimulated (chemically or electrically) to begin dividing and develop into an embryo.

4. Implantation:

• The embryo is implanted into a surrogate mother for further development.

Types of SCNT Applications

1. Therapeutic Cloning:

• To produce stem cells for regenerative medicine.

• These stem cells can replace damaged tissues or treat diseases without risk of immune rejection (as they are genetically identical to the donor).

2. Reproductive Cloning:

• To produce genetically identical individuals.

• Famous Example:

• Dolly the Sheep (1996):

• First mammal successfully cloned using SCNT.

Milestones in SCNT

• Dolly the Sheep:

• Created from a somatic cell nucleus transferred into a denucleated egg, marking a breakthrough in cloning.

• Zhong Zhong and Hua Hua (2018):

• First cloned primates (crab-eating macaques) using SCNT from foetal nuclei.

• A significant advancement in cloning techniques.

Applications of SCNT

1. Biotechnology:

• Producing transgenic animals for medical and agricultural purposes.

2. Medical Research:

• Studying diseases and developing treatments.

3. Conservation Biology:

• Potential use in preserving endangered or extinct species.

4. Reproductive Science:

• Investigating genetic inheritance and reproduction mechanisms.

This method represents a significant leap in both reproductive and therapeutic sciences, demonstrating the potential to address complex biological and medical challenges.