Contribution of Chromosome 14 to Exercise Capacity and Training Responses in Mice

Abstract

Quantitative trait loci for exercise capacity and training-induced changes in exercise capacity were identified previously on mouse Chromosome 14. The aim of this study was to further investigate the role of Chromosome 14 in exercise capacity and responses to training in mice. Exercise phenotypes were measured in chromosome substitution strain mice carrying Chromosome 14 from the PWD/PhJ donor strain on the genetic background of a host C57BL/6J (B6) strain (B6.PWD14). Eight week old female and male mice from both strains completed a graded exercise test to exhaustion to assess intrinsic or baseline exercise capacity. A separate group of 12-week old female and male mice, randomly assigned to sedentary control (SED) or exercise training (EX) groups, completed a graded exercise test before and after a 4-week exercise training period. EX mice completed a 4-week training program consisting of treadmill running 5 days/week, 60 min/day at a final intensity of approximately 65% of maximum. For intrinsic exercise capacity, exercise time and work were significantly greater in female and male B6.PWD14 than sex-matched B6 mice. In the training study, female B6.PWD14 mice had higher pre-training exercise capacity than B6 mice. In contrast, there were no significant differences for pre-training exercise capacity between male B6 and B6.PWD14 mice. There were no significant strain differences for responses to training. These data demonstrate that PWD/PhJ alleles on Chromosome 14 significantly affect intrinsic exercise capacity. Furthermore, these results support continued efforts to identify candidate genes on Chromosome 14 underlying variation in exercise capacity.

Keywords: chromosome substitution strain; genetic; inbred mice; quantitative trait loci (QTL); sex differences; treadmill running.

FIGURE 1

Endurance exercise capacity expressed as time (A) and work (B) in female and male inbred C57BL/6J and B6.PWD14 mice. The chromosome substitution strain (CSS) mice used in this study are based on the C57BL/6J background and carry Chromosome 14 from the PWD/PhJ (B6.PWD14) strain. All mice performed a graded run-to-exhaustion endurance exercise test; exercise capacity was expressed as time (minutes) and work (kg⋅m). Values are expressed as mean ± SD. n = 6 per group. ^∗P < 0.05 significantly different from females of the same strain; ^†P < 0.05 significant strain effect vs. B6.

FIGURE 2

Pre-training exercise capacity and responses to training in female and male inbred C57BL/6J and B6.PWD14 mice. Pre-training exercise capacity and responses to training are expressed as time (minutes) (A,B) and work (kg⋅m) (C,D). The 4-week exercise training program consisted of treadmill running 5 days/week, 60 min/day at a final intensity equivalent to approximately 65% of the maximal work-load (speed and incline) attained during the initial graded treadmill test. All mice performed a graded exercise test to exhaustion before and after 4 weeks of exercise training. B6.PWD14: CSS based on the C57BL/6J background and carry Chromosome 14 from the PWD/PhJ (B6.PWD14) strain. Values are expressed as mean ± SD. n = 5–6 per group. ^∗P < 0.05 significantly different from females; ^†P < 0.05 significant strain effect vs. B6.