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Animal models of complex diseases: an initial strategy
Steven Loyal Britton1, Lauren Gerard Koch
1Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan 48109, USA. brittons@med.umich.edu
IUBMB Life
|October 6, 2005
Summary
Artificial selection for aerobic capacity in rats created distinct lines differing in health. Lower running capacity correlated with disease risk factors, while higher capacity indicated improved cardiovascular and metabolic health.
Area of Science:
- Evolutionary Biology
- Physiology
- Disease Pathogenesis
Background:
- The rise in atmospheric oxygen ~2 billion years ago is linked to the evolution of complex life.
- This oxygen increase may also play a role in the development of complex diseases.
Purpose of the Study:
- To investigate the association between aerobic capacity and complex disease risk.
- To test if artificial selection for running capacity can create lines with contrasting health profiles.
Main Methods:
- Artificial selection for low and high aerobic treadmill running capacity in rats over eleven generations.
- Comparison of physiological and metabolic parameters between the selected lines.
Main Results:
- Achieved a 347% difference in running capacity between the low and high aerobic lines.
- The low-running line exhibited increased visceral adiposity, blood pressure, insulin, and triglycerides.
- The high-running line showed enhanced maximal oxygen uptake (VO2max), running economy, cardiac function, and nitric oxide-induced vasodilation.
Conclusions:
- Aerobic running capacity is strongly associated with markers of health and disease risk.
- Artificial selection can effectively model the relationship between physiological traits and complex diseases.