What are Genetically Engineered Mice? Types of Genetically Engineered Mice Why Mice and not Monkeys or Pigs? The Science - How are Genetically Engineered Mice Made? Role of Biotechnology Uses of Genetically Engineered Mice Examples of Genetically Engineered Mice Genetically Engineered Animals in Development Bibliography

The mouse is a unique animal with many uses in the research lab. They are used to test toxicity of drugs and other substances. They are also used to produce therapeutic products, such as monoclonal antibodies. Since the 1980s, special varieties of genetically engineered mice have been available for researchers.

What are Genetically Engineered Mice?

Genetically engineered mice are designed for the study of certain conditions arising from specific genetic change. They allow researchers to study how a gene affects the progression of a disease and to discover the unknown processes a particular gene may control.

Traditionally, researchers have had to study diseases using tissue culture in the lab. But the complex interactive processes of living mammals are not reproducible outside of the living organism. Ultimately, genetically engineered mice offer more accurate analysis of a disease or treatment since they can take into account genetic, environmental, and other factors that may interact with living organisms throughout their life cycle.

For example, a mouse that has been engineered to have an increased genetic susceptibility to tumour development would allow researchers to observe the development of tumours, weigh environmental and genetic factors in their progression, and test different methods of treatment accordingly.

Types of Genetically Engineered Mice

Generally, genetically engineered mice are called either transgenic mice or "knockout" mice. The terms allude to the method with which they are created.

Transgenic mice:
Any animal whose genetic composition has been altered by the addition of foreign DNA is said to be transgenic. Transgenic mice usually have had the incorporation of known human disease genes. They can be designed to develop conditions such as Alzheimer's disease and tumours.

Transgenic mice are created through a method called DNA microinjection.

Learn more about DNA Microinjection

Knockout mice:
These mice have had certain genes "knocked out" or disabled to observe the effects of such changes. The p53 (a gene thought to play a key role in tumour suppression) knockout mice and the cystic fibrosis mice are examples of knockout mice. Most of the recent biotechnology advances in genetically engineered mice have been made in the creation of knockout mice.

Knockout mice are created through embryonic stem cell-mediated gene transfer.

Learn more about Embryonic Stem Cell-Mediated Transfer

Why Mice and not Monkeys or Pigs?

Mice are used extensively for research purposes because of the similarity of their genetic make-up to human beings.

Almost all human genes have mouse equivalents and studying how the genes work in mice is often the most effective way of discovering the gene's role in human health and disease.

Also, mice are small, easy to house, have a short life span, and reproduce readily. As a result, they are ideal for observing a disease over a life cycle.

The Science - How are Genetically Engineered Mice Made?

DNA Microinjection:
In this process, many copies of DNA are inserted into a fertilized mouse egg. Mice born from these eggs are tested to see if they have the added DNA. These mice are then mated with regular mice and this mating will produce some mice with a stable integration of the added DNA.

Embryonic Stem Cell-mediated Gene Transfer:
In this process, a desired gene is isolated, copied, and genetically modified so that it no longer works. This defective gene is inserted into mouse embryonic stem (ES) cells. Through homologous recombination, the defective gene finds and swaps places with the normal version of that same gene. The cells are tested for the inserted genes and the ones that test positive are injected into a female mouse (surrogate mother). When the pups are born, some will have the defective (or "knockout") gene. Further breeding of these mice results in offspring that carry the defective genes.

Role of Biotechnology

Biotechnology has been essential in the development of genetically engineered mice. Without recombinant DNA technology and tissue culture techniques, the creation of these mice would not have been possible.

In particular, two key biotechnology advances in the 1980s are used in the creation of knockout mice:

• The development of a method that allowed researchers to grow mouse embryonic stem (ES) cells in culture under conditions that allow the cells to remain undifferentiated indefinitely. ES cells have the ability to become any tissue in the body. When culture conditions changed or the ES cells were returned to their natural environment, they were able to continue their development into various tissues.
  
  
• Homologous recombination. In this process, a DNA segment that is added to a host animal's genome finds an identical, or homologous, sequence of DNA in the host's genome and swaps places with it. This process is useful because it allows scientists to copy and genetically engineer a certain DNA strand to inactivate the normal version of the same DNA strand and re-introduce this defective DNA into the host. This results in the loss of function in the target gene.

Uses of Genetically Engineered Mice

Transgenic and knockout mice are used to study a variety of things, including:

• human genetic diseases,
• tumour development,
• developmental consequences of specific inactivated genes,
• regulation of gene expression,
• the potential to produce therapeutics (by serving as a model for other animals); and,
• the effect of different disease treatments.

Examples of Genetically Engineered Mice

There are thousands of different strains of transgenic and knockout mice. There are mice with immune deficiencies, mice prone to different cancers, mice with Huntington's disease, mice with nervous disorders, even mice susceptible to alcoholism and drug addiction.

The following are a few specific examples:

Name	Genetic change	Research Purpose
"Oncomouse" (also known as the Harvard Mouse)	Addition of a new gene that causes a high percentage of the mice to develop tumours.	Observance of the development of tumours and testing of anti-cancer drugs.
Alzheimer's Mouse	Addition of two DNA sequences which results in protein deposits in the brain, typical of Alzheimer's.	Alzheimer's disease and other neurodegenerative diseases.
p53 Knockout	Tumour suppressor gene p53 is "knocked out," or disrupted with the insertion of other genes.	Useful in cancer research since there may be a link between the p53 gene and the development of tumours in humans.
Cystic Fibrosis Mouse	Targeted mutation of the chloride-channel gene which is the primary cause of cystic fibrosis.	It is used to understand how mutations in the gene lead to cystic fibrosis, to test different drug treatments, and to develop gene therapy strategies.

Genetically Engineered Animals in Development

The lab research of mice has led to advances in genetically engineered livestock. Some animals such as cows and pigs are now genetically engineered to produce human proteins and useful therapeutic products in their blood, milk, or urine. This may then be purified for human use. These animals are "living factories" for manufacturing drugs and drug components.

Some examples are as follows:

Animal	Substance produced
Mouse	100 percent human antibodies.
Sheep	blood coagulation factors.
Pig	human haemoglobin

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