The C57BL/6 mouse, often nicknamed “Black 6” due to its coat color, is the most widely used inbred laboratory strain globally. This small rodent serves as a foundational model organism in biomedical science, providing a standardized system for studying human biology and disease. Its popularity stems from its robust nature, well-documented genetics, and adaptability to various laboratory procedures. The ability to perform highly controlled experiments on a genetically uniform mammal makes the C57BL/6 mouse an indispensable tool for scientific discovery.
Origin and Nomenclature
The C57BL/6 strain was developed in 1921 by geneticist Clarence Cook Little at the Bussey Institute for Research in Applied Biology at Harvard University. Little established the original C57BL line by mating specific mice from the stock of Abbie Lathrop. An inbred strain means that all individuals are essentially genetically identical, achieved through a minimum of 20 generations of brother-sister mating.
The nomenclature, C57BL/6, provides a detailed lineage. The “C” and “57” denote the original strain series, while “BL” indicates its black coat color, the source of its common name. The final designation, “/6,” signifies the specific subline separated from the C57BL strain in 1937. This naming system is important because, over time, substrains like C57BL/6J and C57BL/6N have developed small but significant genetic differences due to spontaneous mutations and genetic drift.
Defining Characteristics of the C57BL/6 Strain
The C57BL/6 mouse is considered a sturdy and adaptable model, which is a major factor in its adoption by laboratories worldwide. They possess a sleek, dark brown to nearly black coat and have a median lifespan in captivity of approximately 27 to 29 months. Their relative ease of breeding further contributes to their widespread use.
Behaviorally, the strain exhibits a moderate temperament, though they are more active and prone to biting when handled than some other docile strains. Male C57BL/6 mice can be aggressive, often establishing a hierarchy in group housing that leads to “barbering,” where a dominant mouse chews the fur off its cage mates. The mice are also more sensitive to pain and cold temperatures than other strains, which researchers must consider when designing experiments.
Primary Research Applications
The standardized genetic profile of the C57BL/6 strain makes it suitable for controlled biomedical studies, minimizing variations that could skew results. Its significance in genetics was cemented when a C57BL/6 substrain was chosen to generate the reference sequence for the entire mouse genome project. This foundational genetic map allows researchers to precisely pinpoint and study the effects of specific genetic mutations or modifications.
In immunology, the strain is a standard model due to its genetic makeup at the Major Histocompatibility Complex (MHC) locus, which dictates how the immune system responds to pathogens. They are useful for studies involving T-cell function and are known for mounting a strong Type 1 T-helper cell (Th1) immune response. The C57BL/6 mouse is also widely used in toxicology and drug testing, as its predictable response to various compounds allows for reliable comparative studies.
Unique Phenotypes and Research Limitations
Despite their utility, C57BL/6 mice possess specific biological quirks, or phenotypes, that researchers must account for, as these traits can limit the generalization of findings. One well-documented trait is age-related hearing loss, known as presbycusis, which begins relatively early in life. This makes them an excellent model for studying the human condition, but it is a factor to consider in long-term behavioral or neurological studies.
The strain is also highly susceptible to developing diet-induced obesity and related metabolic issues, such as type 2 diabetes, when fed a high-fat diet. This makes them an ideal model for metabolic syndrome research, though their metabolic baseline differs from other strains. Furthermore, C57BL/6 mice display a preference for consuming alcohol voluntarily, making them a common model for studying addiction and the neurological basis of substance use disorders. While these fixed characteristics benefit the study of specific conditions, they also represent limitations when translating research findings broadly across species.