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Inbred C57BL/6J and C57BL/6N mice exhibit differential vascular dysfunction compared with outbred UM-HET3 mice
Mostafa Sabouri1,2, Xiangyu Zheng1, Bryan J Irwin1
1Nutrition and Integrative Physiology, Florida State University, Tallahassee, Florida, United States.
American Journal of Physiology. Heart and Circulatory Physiology
|December 24, 2025
Summary
Biomedical research using C57BL/6 mice should consider substrain differences. Outbred UM-HET3 mice exhibit superior vascular function without increased variability, offering a promising alternative to inbred strains.
Area of Science:
- Cardiovascular Research
- Animal Models in Biomedical Research
- Vascular Physiology
Background:
- Inbred C57BL/6 mice are standard in research, with C57BL/6J and C57BL/6N substrains often used interchangeably.
- Subtle genetic differences between C57BL/6 substrains can impact experimental outcomes, particularly in vascular studies.
- Understanding these differences is crucial for accurate interpretation of research findings.
Purpose of the Study:
- To compare vascular function between C57BL/6J and C57BL/6N mouse substrains.
- To evaluate the impact of inbreeding on vascular function by comparing C57BL/6 substrains with the outbred UM-HET3 mice.
- To assess the suitability of UM-HET3 mice as an alternative to inbred C57BL/6 mice in biomedical research.
Main Methods:
- Vascular function assessment in C57BL/6J, C57BL/6N, and UM-HET3 mice.
- Measurements included systolic blood pressure, aortic stiffness, vasodilation responses (acetylcholine-mediated and flow-mediated), and aortic structural characteristics.
- Comparison of vascular parameters and measurement variability across the different mouse strains.
Main Results:
- C57BL/6N mice exhibited lower systolic blood pressure and aortic stiffness compared to C57BL/6J mice.
- Flow-mediated vasodilation was greater in C57BL/6N mice than in C57BL/6J mice.
- UM-HET3 mice demonstrated generally superior vascular function compared to both C57BL/6 substrains, with no increase in measurement variability.
Conclusions:
- Significant differences in vascular function exist between C57BL/6J and C57BL/6N substrains, with C57BL/6N showing better vascular health.
- Outbred UM-HET3 mice possess enhanced vascular function compared to inbred C57BL/6 mice.
- UM-HET3 mice represent a viable alternative to inbred strains in biomedical research due to their superior vascular function and comparable measurement variability.

