What is a knockout mouse?

Short answer: A knockout mouse is a science-bred mouse that has a specific gene or regulatory region of the genome deleted.

More detail:

Genetics is the study of how traits are passed from generation to generation, and specifically focuses on how changes in the DNA encoding those traits can lead to individual trait differences and disease. Simply put, a phenotype is the observable outcome of a particular gene. For example, you could have a gene leading to brown or blue pigment in your eyes. If one variant of this gene (or allele) codes for blue eyes and the other codes for brown, you could end up with a brown-eyed “phenotype.” (Click here for a better explanation of alleles and dominant/recessive inheritance; for a better explanation of the genotype-phenotype distinction, check this out).

Scientists are able to figure out what different genes do by introducing mutations into the genome and then asking “what broke?” and “how did it break?” by screening for particular phenotypes. For example, you can introduce mutations with radiation and then look for cells that divide more slowly. Then, isolate these cells and ask “which genes were destroyed or changed when I introduced the mutations that caused slow cell division?”

Through screens or through genome wide association studies (which use SNPs in the human genome to track disease-associated regions), we’ve discovered many genes involved in disease processes.

When we want to study those genes further, though, we want to know exactly what the gene does and how it works with other genes to drive disease or other cellular processes. To study these, scientists often turn to model organisms and genetic knockouts.

A model organism is an organism with a fast reproductive cycle and conserved processes (as in: development in frogs approximates the same steps of development that happens in many other animals and thus represents a good system in which to study those steps). These organisms are well defined (we know a lot about them), and they are carefully bred. Choice of a model organism is guided by what process a scientist is studying; some common examples include worms, fruit flies, frogs, rats, and mice.

Model organisms allow researchers to do thoroughly controlled scientific studies that would be highly unethical in humans (where we cant manipulate the genome or define breeding pairs). These experiments allow us to understand basic processes in biology as well as learn about new drugs and therapies.

Model organisms can be used to study the impact of a gene on development and physiology through a genetic knockout. Scientists can engineer the genomes of some model organisms such as flies or mice, and can selectively delete a gene from specific tissues or the entire organism. These mutants are called “conditional knockouts” and “knockouts,” respectively, because the gene has been knocked out of the organism’s genome.

Many knockout mice are already available to help researchers study processes from cancer to neurodegeneration.


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