Knockout mice are engineered laboratory mice with one or more genes inactivated. This modification provides scientists with a powerful tool to investigate specific gene roles within a living organism. By understanding how a gene’s absence affects the mouse, researchers gain insights into fundamental biological processes and disease mechanisms. These mice are indispensable in biological and medical research.
How Knockout Mice Are Made
The creation of knockout mice involves genetic engineering techniques to disable a target gene. Historically, embryonic stem (ES) cells were used. A modified DNA sequence was introduced into ES cells, replacing the functional gene via homologous recombination, ensuring the target gene was no longer expressed.
More recently, CRISPR/Cas9 gene-editing revolutionized knockout mouse creation, offering a precise and efficient way to inactivate genes directly in fertilized eggs. This method disrupts a gene’s sequence, preventing protein production. Modified embryos are then implanted into a surrogate mother, producing offspring with the inactivated gene.
Understanding Gene Roles
A primary application of knockout mice is to unravel individual gene functions. By observing differences between a knockout mouse (lacking a gene) and a normal, wild-type mouse, researchers deduce the gene’s role. If a gene is knocked out and the mouse develops a specific physical or behavioral change, it suggests the gene normally influences that trait.
This comparative analysis identifies a gene’s contribution to an organism’s development, physiology, or behavior. For example, knocking out a metabolism gene might lead to changes in weight or energy regulation. These observations provide direct evidence for the gene’s involvement in specific biological pathways, expanding understanding of genetic contributions to complex systems.
Mimicking Human Illnesses
Knockout mice are engineered as models for human diseases. This is achieved by inactivating a gene in mice associated with a specific human illness. For example, if a human genetic disorder is caused by a non-functional gene, researchers create a mouse with the homologous gene knocked out to replicate the condition.
These disease models allow scientists to study illness progression in a living system, observing symptom development. For instance, a mouse model for cystic fibrosis might exhibit lung abnormalities similar to human patients. Such models provide a controlled environment to investigate disease mechanisms, which is often difficult in humans.
Advancing New Treatments
After creating disease models, knockout mice are instrumental in pre-clinical therapy development and testing. These mice, exhibiting disease-like symptoms, evaluate the efficacy and safety of new drugs, gene therapies, or other interventions. Researchers administer experimental treatments to the mice, observing if symptoms improve or disease progression halts.
This application validates therapeutic strategies before human clinical trials. For example, a new drug for a neurological disorder can first be tested on a knockout mouse model exhibiting similar neurological deficits. These models help identify promising treatments and understand potential side effects, streamlining drug discovery and development.