The C57BL/6 mouse, often called “Black 6” or B6, is the most widely used inbred laboratory mouse strain globally. Its popularity in biomedical research stems from its exceptional genetic uniformity. The consistency of its genetic background minimizes biological variability between individual animals, which is necessary for reliable and reproducible scientific experiments. This standardization allows researchers to attribute observed differences in outcomes to the specific variables being tested.
Origin and Establishment of the Strain
The C57BL/6 strain originated in the early 20th century with geneticist Clarence Cook Little. In 1921, Little developed the strain by crossing mice from a commercial breeder, Abby Lathrop (female N. 57 and male N. 52). This initial breeding established the C57BL line, and the C57BL/6 strain was officially separated from the main colony in 1937.
The strain was created through rigorous, systematic inbreeding, involving repeatedly mating brother-sister pairs over hundreds of generations. This process achieved genetic homogeneity, meaning every mouse within the strain is nearly genetically identical. The C57BL/6 became the first truly successful and standardized inbred strain, establishing a foundational model for laboratory science. Its original colony, C57BL/6J, was maintained at The Jackson Laboratory, with the “J” designating the institution.
Defining Physical and Behavioral Characteristics
The C57BL/6 mouse has a characteristic phenotype, including a dark brown, almost black coat color, which is the source of its common name, “Black 6.” Physically, these mice are robust, long-lived, and display a low susceptibility to spontaneous tumor development compared to other strains.
Behaviorally, the B6 strain is more active and sensitive than other common laboratory strains. They are sensitive to environmental factors like noise and odor, and sometimes display higher levels of aggression. A distinctive trait is their voluntary consumption of alcoholic beverages, which is unusual among laboratory mouse strains.
The strain also displays susceptibility to specific age-related sensory deficits. C57BL/6 mice develop early-onset hearing loss, caused by the gene variant \(Cdh23^{ahl}\). The hearing loss begins around 10 weeks of age, progressing rapidly, especially for high-frequency sounds. This makes them a natural model for studying human age-related hearing impairment.
Genetic Foundation for Research Utility
The C57BL/6 mice became the research standard due to their precisely defined genetic background. Their genome was the second mammalian genome fully sequenced, following the human genome, establishing it as the reference strain for mouse genetics. This sequencing provides researchers with a genetic roadmap, facilitating advanced genetic manipulation techniques.
This genetic uniformity minimizes non-experimental variables. Researchers can introduce a single genetic modification, such as a gene knockout, and know that any resulting change in phenotype is directly attributable to that modification. This makes the B6 strain the preferred background for developing genetically engineered mouse models, including transgenic or knockout models.
The strain possesses inherent genetic traits that predispose it to certain conditions, making it valuable for modeling specific human diseases. For instance, C57BL/6 mice are susceptible to diet-induced obesity and type 2 diabetes when fed a high-fat diet. This response makes them a widely utilized model for investigating metabolic disorders and testing anti-obesity drugs. They are also susceptible to atherosclerosis, making them useful in cardiovascular biology studies.
Primary Applications in Scientific Modeling
The predictable genetic and phenotypic traits of the C57BL/6 strain have made it indispensable across numerous scientific fields. In oncology, the B6 mouse is used for modeling tumor immunity and testing cancer therapies. They serve as a standard background for syngeneic tumor models, where the cancer cells and the host mouse are genetically matched, allowing for accurate study of the immune system’s interaction with the tumor.
Immunology relies on the B6 strain because of its robust type 1 helper T cell (Th1) immune response. This strong cell-mediated immunity and high natural killer (NK) cell activity make them models for studying infectious diseases, vaccine efficacy, and autoimmune conditions. Their distinct immune profile helps researchers understand how genetic background influences response to infection or therapeutic agents.
In neurobiology, the B6 mouse is employed to study complex behaviors and neurological disorders. Their susceptibility to morphine addiction and voluntary alcohol consumption make them valuable for addiction research and understanding the genetic basis of substance use disorders. Their well-characterized genome and behavioral patterns support studies in areas like neurodegenerative diseases and psychiatric illness.