An Inbred Rat Model of Exercise Capacity: The Path to Identifying Alleles Regulating Variation in Treadmill Running Performance and Associated Phenotypes
Aerobic exercise tests measure the integrative ability of multiple physiological systems to adapt to acute aerobic exercise and are often used to determine physical fitness, assess overall health, and predict mortality. While the associations between physical fitness, aerobic performance, and overall health are well known, the underlying genetic factors involved are poorly understood. Identifying these underlying genetic factors is therefore an essential step toward a greater understanding of the relationship between physical fitness and health. Two inbred rat strains divergent for treadmill aerobic running capacity (ARC) were previously identified, the low performing Copenhagen (COP) and the high performing DA rats. An F2(COPxDA) population was used to identify ARC quantitative trait loci (QTLs) on rat chromosome 16 (RNO16) and the proximal portion of rat chromosome 3 (RNO3). Three congenic rat strains were bred to further investigate these ARC QTLs by transferring RNO16 and the proximal portion of RNO3 from DA rats and RNO16 from COP rats into the respective genetic backgrounds of COP and DA rats. These rat strains were named COP.DA(chr 16), COP.DA(chr 3), and DA.COP(chr 16), respectively. COP.DA(chr 16) and DA.COP(chr 16) rats had significantly different ARC compared to COP and DA rats, respectively. COP.DA(chr 3) rats had increased, although not significant, ARC compared to COP rats. Subcutaneous abdominal fat, fasting triglyceride concentrations, cardiac diastolic function, and exercise-induced changes in energy substrates were identified as potential intermediate phenotypes to help explain the differences in exercise performance between COP and DA strains. While the colocalization of these phenotypes and the ARC QTLs may be coincidental, it is also possible that these differences in energy balance and cardiac function may be associated with the superior running performance of DA rats. Gene expression and molecular network analysis identified twelve potential gene candidates as being the underlying genetic determinants of the intermediate phenotype and ARC strain differences observed between COP, DA, and their respective congenic strains.
School:University of Toledo Health Science Campus
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:genomics cardiovascular rat models metabolism exercise treadmill running
Date of Publication:01/01/2007