The C57BL/6 mouse is the most widely utilized inbred laboratory mouse strain in biomedical research. Its standardized and well-characterized genetic background makes it a fundamental tool for scientific investigations. This strain serves as a reference genome, providing a consistent biological foundation for genetic studies. An inbred strain refers to animals that are genetically identical, achieved through many generations of sibling mating.
Genetic Background and History
The C57BL/6 strain originated from a mouse acquired by Clarence Cook Little in 1918. Through a rigorous process of inbreeding, involving more than 20 generations of brother-sister mating, Little established genetically uniform mouse lines in the 1920s. This methodical inbreeding aimed to create a population of animals with minimal genetic variability, which significantly reduces experimental noise and improves the reproducibility of research findings.
Two major substrains emerged from these early efforts: C57BL/6J, maintained by The Jackson Laboratory, and C57BL/6N, distributed by the National Institutes of Health. While both substrains share a common ancestry, subtle genetic differences have accumulated over decades due to independent breeding and genetic drift. These minor distinctions can sometimes lead to varying experimental outcomes, prompting researchers to specify the exact substrain used in their studies.
Key Research Applications
C57BL/6 mice are widely employed across scientific disciplines.
Immunology
In immunology, their immune system exhibits a strong T helper 1 (Th1)-biased response, making them a model for studying infectious diseases, inflammatory conditions, and vaccine efficacy. They are also used to investigate the body’s response to bacterial and viral pathogens.
Neuroscience
In neuroscience, these mice are valuable for studying addiction, partly due to their innate preference for alcohol consumption and their responsiveness to morphine. They also serve as models for examining anxiety-related behaviors and exploring the mechanisms of neurodegenerative diseases.
Metabolic Disorders
The C57BL/6 strain is susceptible to diet-induced obesity, type 2 diabetes, and atherosclerosis when fed a high-fat diet. This makes them a model for research into metabolic disorders, allowing scientists to investigate the genetic and environmental factors contributing to these widespread conditions. Studies on insulin resistance and lipid metabolism often rely on this strain.
Oncology
In oncology, C57BL/6 mice are used as the background strain for creating genetically engineered mouse models (GEMs). These models involve specific gene deletions or insertions, allowing researchers to study the function of particular genes in cancer initiation and progression. The genetic consistency of the C57BL/6 background ensures that any observed phenotypic changes are attributable to the engineered genetic modifications.
Distinct Phenotypic Characteristics
C57BL/6 mice exhibit distinct physiological and behavioral characteristics.
Physiological Traits
Physiologically, they are recognized by their black coat color. A notable physiological feature is their predisposition to age-related hearing loss, which is linked to a mutation in the Cdh23 gene. This genetic alteration causes progressive degeneration of hair cells in the inner ear.
These mice also show a relatively high incidence of microphthalmia, a condition characterized by abnormally small eyes. Their bone density characteristics are well-documented, often serving as a reference for studies on bone health and disease. These consistent physiological traits provide a stable background for various biomedical investigations.
Behavioral Traits
Behaviorally, C57BL/6 mice tend to display higher anxiety levels in standard behavioral tests compared to other strains. They also show a pronounced voluntary consumption of both alcohol and morphine, making them useful in addiction research. Another common behavioral trait observed in this strain is barbering, where mice pluck their own fur or that of their cagemates, which can sometimes lead to patches of hair loss.
Immunological Profile
Immunologically, the C57BL/6 strain displays a strong pro-inflammatory (Th1) immune response. Their immune cells, particularly T helper 1 lymphocytes, are predisposed to produce cytokines like interferon-gamma. This robust inflammatory response contributes to their utility in studies of infectious diseases and autoimmune conditions.
Considerations in Experimental Design and Husbandry
Working with C57BL/6 mice requires specific considerations in both husbandry practices and experimental design.
Husbandry Practices
In terms of husbandry, these mice can be sensitive to environmental factors such as noise and light, partly due to their carriage of an albino gene. Maintaining a stable and quiet environment helps to reduce stress and variability in experimental outcomes. Group-housed male C57BL/6 mice are known to exhibit aggression, which can lead to fighting and injuries. Researchers often need to house males individually or closely monitor group dynamics to prevent aggression-related stress and confounding variables in studies. Diet considerations are also important, as their propensity for diet-induced obesity necessitates careful control of caloric intake, especially in metabolic studies.
Experimental Design
From an experimental design perspective, researchers must account for the strain’s known phenotypes. For instance, studies involving auditory cues must consider their inherent age-related hearing loss, particularly in older animals, to avoid misinterpreting results. Their naturally high anxiety levels can also be a confounding variable in behavioral studies not specifically focused on anxiety, requiring careful experimental controls. The choice between substrains, such as C57BL/6J and C57BL/6N, is also paramount. Subtle genetic differences between these substrains can influence various traits, including immune responses, metabolic profiles, and neurological phenotypes. Therefore, selecting the appropriate substrain for a specific research question is an important step in designing experiments to ensure the relevance and accuracy of findings.