Genetically modified mouse

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Genetically modified mice are mice that have had their genomes altered through genetic engineering. These modifications allow researchers to study gene function and regulation, model human diseases, and test potential therapies in a controlled environment. Genetically modified mice are central to biomedical research and have contributed to numerous scientific advances.

History

The development of genetically modified mice began in the 1970s with the advent of recombinant DNA technology. The first transgenic mice, mice that had foreign DNA inserted into their genome, were created in 1980. This was followed by the creation of knockout mice, animals in which a specific gene has been inactivated, in the late 1980s. Since then, the techniques for manipulating the mouse genome have become increasingly sophisticated, allowing for more precise genetic modifications.

Types of Genetically Modified Mice

There are several types of genetically modified mice, each serving different purposes in research:

• Transgenic mice: These mice carry foreign genes that have been deliberately inserted into their genome. Transgenic mice are used to study the function of genes and how their expression affects the organism.
• Knockout mice: In these mice, one or more genes have been inactivated. Knockout mice are valuable for understanding the role of specific genes in development, physiology, and disease.
• Knock-in mice: These mice have had a gene sequence or mutation introduced into a particular locus. This technique is used to study the effects of specific gene mutations.
• Conditional knockout mice: These mice allow for the inactivation of genes in specific tissues or at specific times during development. This is crucial for studying genes that are essential for survival, as their complete knockout would result in embryonic lethality.

Creating Genetically Modified Mice

The creation of genetically modified mice involves several steps:

1. Design and Construction of the Genetic Modification: The first step is to design the DNA construct that will be introduced into the mouse genome. This involves selecting the gene to be modified and the type of modification (e.g., insertion, deletion, mutation).

2. Introduction of the DNA into Mouse Embryos: The DNA construct is then introduced into mouse embryos, typically at the one-cell stage, using techniques such as microinjection, electroporation, or viral vectors.

3. Implantation of Embryos into Surrogate Mothers: The modified embryos are implanted into the uteri of surrogate mother mice, where they develop into live offspring.

4. Screening for Genetically Modified Offspring: The offspring are screened to identify those that carry the genetic modification. This is usually done using polymerase chain reaction (PCR) or Southern blot analysis.

Applications

Genetically modified mice have a wide range of applications in biomedical research, including:

• Disease Modeling: They are used to create models of human diseases, such as cancer, neurodegenerative disorders, and cardiovascular diseases. These models are invaluable for understanding disease mechanisms and for testing new treatments.
• Gene Function: By observing the effects of gene modifications, researchers can infer the function of genes and the biological pathways they are involved in.
• Drug Development: Genetically modified mice are used in preclinical testing of new drugs to assess their efficacy and safety.

Ethical Considerations

The use of genetically modified mice raises ethical concerns, including animal welfare and the potential for unintended consequences of genetic modifications. Researchers must adhere to strict ethical guidelines and regulatory requirements when creating and using genetically modified mice.