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Sex differences in voluntary running behavior between C57BL/6 and BALB/cJ mouse strains do not correspond to changes
N Amiri1,2, H Zhang1, R McMillan1
1Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, Virginia, USA.
Physiological Reports
|October 11, 2025
Summary
Exercise adaptations vary by sex and genetics. This study in mice reveals distinct physiological responses to running, emphasizing the need to consider these factors in research.
Area of Science:
- Exercise physiology
- Metabolic adaptations
- Animal models
Background:
- Exercise adaptations exhibit significant variability influenced by sex and genetic background.
- Understanding these differences is crucial for interpreting metabolic and physiological responses to physical activity.
Purpose of the Study:
- To investigate sex- and strain-specific differences in physiological adaptations following voluntary wheel running exercise.
- To examine submaximal and maximal oxygen consumption (VO2), respiratory exchange ratio (RER), and body composition in C57BL/6 and BALB/cJ mice.
Main Methods:
- Four weeks of voluntary wheel running in male and female C57BL/6 and BALB/cJ mice.
- Sub-maximal and maximal treadmill tests conducted in a metabolic chamber.
- Analysis of running volume, VO2, RER, body composition, and blood lactate levels.
Main Results:
- Running volume varied significantly across sexes and strains, not consistently predicting physiological changes.
- Female C57BL/6 mice showed higher submaximal VO2 compared to males and female BALB/cJ mice.
- Male BALB/cJ mice exhibited enhanced endurance capacity and a decrease in RER during maximal testing; female C57BL/6 mice improved body composition.
Conclusions:
- Sex and strain are critical factors influencing exercise adaptations in mice.
- Standard VO2 testing may not fully capture adaptive responses to voluntary wheel running.
- Future research should account for sex- and strain-specific variations in exercise studies.

