The laboratory mouse, Mus musculus, is the most common mammalian model organism used in biomedical research worldwide. This reliance is deliberate, allowing researchers globally to use animals with known, predictable characteristics, ensuring the reproducibility and comparability of scientific findings. The standardization transforms the common house mouse into a sophisticated scientific tool for investigating complex human diseases.
Why Mice Are the Primary Mammalian Model
Mice are chosen for scientific study due to a combination of biological and practical attributes. Genetically, mice share a remarkable similarity with humans; approximately 90% of genes associated with disease are identical to those in humans. This genetic overlap means that many biological processes and disease mechanisms operate similarly, making the mouse an effective proxy for human physiology.
The practicality of using mice is a significant factor in their selection. Their small size makes them economical to house and maintain in large numbers, which is necessary for rigorous statistical testing. Mice also have a rapid reproductive cycle, with a gestation period of only 19 to 21 days. This short generation time and accelerated lifespan allow scientists to conduct longitudinal studies on aging and disease progression in a manageable timeframe.
Defining Standardized Laboratory Strains
Standardized laboratory strains are categorized primarily by their breeding strategy. Inbred lines are created through a minimum of 20 generations of brother-sister mating, resulting in animals that are nearly 99% genetically identical and homozygous. This genetic uniformity minimizes variability between individual mice, allowing researchers to attribute experimental outcomes to the tested variable rather than genetic differences.
Two widely used inbred strains are C57BL/6 and BALB/c, each suitable for specific studies. C57BL/6 mice, often called “Black 6” or “B6,” have a black coat and are frequently used as the genetic background for creating genetically modified mice due to their robustness and ease of breeding. In contrast, BALB/c mice have an albino coat and are favored in oncology and immunology research because they tend to develop tumors more readily and exhibit a different immune response profile. Conversely, outbred stocks are bred to maximize genetic diversity and heterozygosity. These outbred mice are employed in toxicology and safety testing, where a range of responses is desired to better reflect the genetic heterogeneity of the human population.
Engineering Mice for Targeted Research
Beyond the standardization achieved through breeding, researchers employ advanced genetic engineering to modify mice for specific experimental goals. Transgenic mice are created by inserting foreign DNA, such as a human gene, into the mouse genome, which allows scientists to study the function of that gene or the effects of its overexpression.
Another sophisticated model is the knockout mouse, where a specific gene is inactivated or deleted from the genome. By removing a gene, researchers observe the resulting biological changes and determine the gene’s function, often using technologies like CRISPR for precise gene editing. The development of humanized mice represents the most advanced form of engineering, where immunodeficient mice are modified to carry human genes, cells, or tissues. This is achieved by replacing mouse genes with human equivalents or engrafting human immune cells, creating a model that can more accurately predict human-specific drug responses, especially in areas like immunotherapy.
Key Areas of Scientific Application
Standardized and engineered mouse models underpin research across multiple medical fields, providing a platform for studying disease and testing therapies. In oncology, mouse models are indispensable for understanding cancer development and evaluating novel treatments. This includes using humanized mice to test immunotherapies, where the mouse is engrafted with a human immune system and human tumor cells to observe their interaction.
Immunology research relies on specific inbred strains, such as C57BL/6 and BALB/c, which have distinct immune system characteristics, to study vaccine efficacy and autoimmune disorders. For instance, BALB/c mice are known for a stronger antibody-mediated immune response, making them useful for studying conditions where this response is dominant. Furthermore, the ability to create knockout mice that lack specific immune components has been instrumental in dissecting the complex mechanisms of the immune system. Mouse models are also widely used in toxicology and drug testing, where both genetically uniform inbred lines and diverse outbred stocks are used to assess the safety and efficacy of new pharmaceutical compounds. The ability to model human disease and test therapeutic agents in a controlled, living system before human trials is a crucial step in the drug development pipeline.