Black Mice in Research: Traits, Behavior, and Applications

Laboratory mice are essential to biomedical research, offering insights into genetics, disease mechanisms, and potential treatments. Among the many strains used, black-coated mice stand out due to their well-documented genetic background and predictable physiological responses. Their reliability makes them ideal for controlled experiments, allowing researchers to select the most appropriate models for various studies.

Genetic Traits of C57BL/6

The C57BL/6 strain is one of the most extensively studied in biomedical research due to its well-characterized genome and high genetic stability. Originally developed in the early 20th century by Clarence Cook Little, this inbred strain has undergone over 200 generations of brother-sister matings, resulting in a remarkably uniform genetic background. This consistency minimizes variability in experimental outcomes, making it a preferred model for studies requiring reproducibility. The complete sequencing of its genome, first published in Nature in 2002, further solidified its role as a reference strain for genetic and molecular research.

A key genetic feature of C57BL/6 mice is their predisposition to specific phenotypic traits linked to gene variants. For example, they carry mutations in the Nnt (nicotinamide nucleotide transhydrogenase) gene, affecting mitochondrial function and glucose homeostasis, making them a common model for diabetes research. They also exhibit a polymorphism in the Oprm1 gene, which encodes the mu-opioid receptor, influencing their response to pain and analgesics—an important factor in pharmacological studies.

These mice are also prone to age-related hearing loss due to mutations in the Cdh23 gene, making them valuable for auditory research. Their susceptibility to diet-induced obesity, linked to variations in Lepr and Pparg, makes them indispensable for metabolic disorder studies.

Physiology and Distinguishing Features

C57BL/6 mice have a distinct physiological profile shaped by their genetic background, affecting metabolism, sensory capabilities, and physical traits. Their black coat results from a mutation in the nonagouti (a) gene, which eliminates the agouti signaling protein that regulates fur pigmentation. While coat color has little direct impact on research outcomes, it serves as a genetic marker and may influence thermoregulation in temperature-sensitive studies.

Metabolically, these mice have a higher propensity for adiposity on high-fat diets due to polymorphisms in Lepr and Pparg, making them a standard model for obesity and metabolic syndrome research. Their lower baseline energy expenditure contributes to increased fat accumulation under energy-dense conditions. Additionally, impaired insulin secretion from an Nnt gene deficiency affects mitochondrial function in pancreatic beta cells, making them useful for diabetes research.

Their sensory physiology also presents unique attributes. They are prone to age-related hearing loss due to Cdh23 mutations, a condition that typically begins around six months of age. Their vision is adequate for standard laboratory conditions but has lower retinal contrast sensitivity than strains like BALB/c, influencing responses in visually demanding tasks.

Thermoregulatory differences further distinguish C57BL/6 mice. Their lower basal body temperature and higher susceptibility to cold stress impact studies involving environmental adaptation. Their black fur absorbs more radiant heat than lighter-colored strains, which can influence thermal homeostasis. Additionally, strain-specific variations in brown adipose tissue activity play a role in non-shivering thermogenesis, relevant in energy expenditure and cold adaptation research.

Common Uses in Research

C57BL/6 mice are widely used in biomedical research due to their genetic stability and disease susceptibility. Their applications span immunology, neuroscience, and oncology, providing critical insights into human health.

Immunology

C57BL/6 mice are essential in immunological research due to their Th1-biased immune system, which favors cell-mediated responses. This makes them ideal for studying infections, autoimmune diseases, and vaccine efficacy. Their strong cytotoxic T-cell activity supports research on viral and bacterial infections, including influenza, tuberculosis, and HIV.

They are also widely used in inflammation and autoimmune disease models, such as experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Their genetic predisposition to chronic inflammation aids research into immune dysregulation. Additionally, they serve as the genetic background for many transgenic and knockout models used in cytokine signaling, immune checkpoint regulation, and immunotherapy studies.

Neuroscience

C57BL/6 mice are valuable in neuroscience due to their well-documented behavioral traits and genetic predisposition to neurological conditions. Their high baseline activity and exploratory behavior make them suitable for cognitive and behavioral studies, including learning, memory, and anxiety research. They perform well in maze-based tasks, such as the Morris water maze and radial arm maze, which assess spatial learning.

They are commonly used in neurodegenerative disease research, including studies on Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS). Their susceptibility to age-related hearing loss makes them a useful model for auditory neuroscience. Additionally, their response to pain and analgesics, influenced by Oprm1 gene polymorphisms, supports pain research, including opioid sensitivity and addiction studies.

Oncology

C57BL/6 mice play a critical role in cancer research due to their compatibility with syngeneic tumor models and well-characterized immune system. They are frequently used in studies of melanoma, lung cancer, and lymphoma, as well as genetically engineered models that develop spontaneous tumors. Their strong immune response makes them valuable for immuno-oncology research, including checkpoint inhibitor therapies and CAR-T cell treatments.

A key contribution to oncology is their use in the B16 melanoma model, which helps researchers study tumor growth, metastasis, and immune evasion. Additionally, they serve as the background strain for many genetically modified cancer models, such as those carrying Tp53 or Kras mutations, which are crucial for studying tumorigenesis and targeted therapies.

Behavioral Observations

C57BL/6 mice exhibit a distinct behavioral profile, making them a preferred strain for studies requiring consistent responses. They have a high exploratory drive, often displaying increased locomotor activity in open-field tests. This curiosity makes them useful in behavioral assays for anxiety, spatial learning, and novelty-seeking tendencies.

Their social interactions tend to be less aggressive than other strains, though dominance hierarchies still emerge in group housing. Males establish rankings through subtle posturing and occasional skirmishes, though they generally exhibit lower aggression than BALB/c or DBA/2 strains. This makes them suitable for studies on social behaviors, including autism spectrum disorder models.

Variations in Other Black Mouse Strains

While C57BL/6 mice are the most widely used black-coated strain, other black mouse strains have unique genetic and physiological traits suited to different research areas. Understanding these variations helps researchers select the most appropriate model for specific studies.

C57BL/10 mice, which share ancestry with C57BL/6, have distinct immunological and metabolic characteristics. Unlike C57BL/6, they do not carry the Nnt mutation affecting mitochondrial function, making them preferable for studies requiring normal glucose metabolism.

DBA/2 mice differ significantly in behavioral and sensory traits, experiencing early-onset hearing loss due to a different Cdh23 mutation. They also exhibit higher baseline anxiety and lower pain tolerance, influencing their use in behavioral neuroscience.

129 black-coated substrains, such as 129S1/SvImJ, present distinct genetic attributes. These strains are frequently used in gene-targeting studies due to their embryonic stem cell compatibility, facilitating the development of numerous knockout models. However, they show lower exploratory activity compared to C57BL/6, affecting behavioral research outcomes.

By understanding the specific traits of various black mouse strains, researchers can make informed decisions about which model best suits their investigative needs, ensuring more accurate and reproducible findings.