Genetic architecture of voluntary exercise in an advanced intercross line of mice

Kelly SA, Nehrenberg DL, Peirce JL, Hua K, Steffy BM, Wiltshire T, Pardo-Manuel de Villena F, Garland T Jr, Pomp D. Genetic architecture of voluntary exercise in an advanced intercross line of mice. Physiol Genomics 42: 190-200, 2010. First published April 13, 2010; doi: 10.1152/physiolgenomics.00028.2010.-Exercise is essential for health, yet the amount, duration, and intensity that individuals engage in are strikingly variable, even under prescription. Our focus was to identify the locations and effects of quantitative trait loci (QTL) controlling genetic predisposition for exercise-related traits, utilizing a large advanced intercross line (AIL) of mice. This AIL (G(4)) population originated from a reciprocal cross between mice with genetic propensity for increased voluntary exercise [high-runner (HR) line, selectively bred for increased wheel running] and the inbred strain C57BL/6J. After adjusting for family structure, we detected 32 significant and 13 suggestive QTL representing both daily running traits (distance, duration, average speed, and maximum speed) and the mean of these traits on days 5 and 6 (the selection criteria for HR) of a 6-day test conducted at 8 wk of age, with many colocalizing to similar genomic regions. Additionally, seven significant and five suggestive QTL were observed for the slope and intercept of a linear regression across all 6 days of running, some representing a combination of the daily traits. We also observed two significant and two suggestive QTL for body mass before exercise. These results, from a well-defined animal model, reinforce a genetic basis for the predisposition to engage in voluntary exercise, dissect this predisposition into daily segments across a continuous time period, and present unique QTL that may provide insight into the initiation, continuation, and temporal pattern of voluntary activity in mammals.