2026.03.09
In preclinical biomedical research, mouse models are indispensable tools, with CD-1, C57BL/6N, and BALB/c being among the most frequently utilized strains. Their genetic backgrounds influence experimental outcomes, making strain selection critical for study design. This article summarizes their origins and highlights preferences in clinical research based on empirical evidence.
CD-1 is an outbred strain derived from Swiss mice, characterized by genetic heterogeneity that mimics human population diversity. It is often employed in general toxicity and behavioral studies due to its robustness and variability . In contrast, C57BL/6N is an inbred substrain of the C57BL/6 lineage, which originated in the early 20th century and has since diverged into multiple substrains (e.g., C57BL/6J) with notable genetic variations. This strain is favored for its well-documented genome and consistency in genetic manipulation. BALB/c, another inbred strain, exhibits substrain differences (e.g., BALB/cJ vs. BALB/cByJ) that affect immune responses, with origins tracing back to albino mice. Its genetic stability makes it ideal for immunology-focused research.
- C57BL/6N: This strain is preferred for studies on metabolism, neurology, and immunology due to its Th1-dominant immune profile, which promotes pro-inflammatory responses. It shows resistance in certain disease models, such as kidney injury and ulcerative colitis, but is susceptible to metabolic disorders like glucose intolerance. Researchers select it for genetic engineering and cancer immunotherapy studies because of its high acceptance of syngeneic tumors and predictable phenotypes . However, substrain differences (e.g., C57BL/6N vs. C57BL/6J) can impact results, necessitating careful selection .
- BALB/c: With a Th2-biased immune response, BALB/c is commonly chosen for allergy, infectious disease, and autoimmune research. It demonstrates heightened susceptibility in models like ovalbumin-induced food allergy, *Cryptococcus neoformans* infection, and dextran sulfate sodium (DSS)-induced colitis, often exhibiting more severe inflammation and organ damage compared to C57BL/6 . This strain is also optimal for vaccine development and respiratory studies, as seen in SARS-CoV-2 and influenza models, due to its pronounced inflammatory outcomes.
- CD-1: As an outbred strain, CD-1 is selected for toxicology, pharmacology, and infection studies where genetic diversity is advantageous. It shows variable resistance in plague models (e.g., bubonic vs. pneumonic) and is used in behavior and transplantation research to capture human-like heterogeneity . Its adaptability in diverse environmental conditions makes it suitable for large-scale safety assessments.
Strain choice hinges on research goals: C57BL/6N offers genetic uniformity for mechanistic studies, BALB/c provides sensitivity in immune-mediated diseases, and CD-1 introduces variability for translational relevance. Understanding these preferences ensures robust and reproducible preclinical data. Always consider substrain variations to optimize model fidelity.
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