Differences in Exercise Capacity and Responses to Training in 24 Inbred Mouse Strains

Abstract

Changes in cardiorespiratory fitness in response to a standardized exercise training protocol differ substantially between individuals. Results from cross-sectional, twin, and family studies indicate genetics contribute to individual differences in both baseline exercise capacity and the response to training. Exercise capacity and responses to training also vary between inbred strains of mice. However, such studies have utilized a limited number of inbred strains. Therefore, the aim of this study was to characterize exercise-training responses in a larger number of genetically diverse strains of inbred mice and estimate the contribution of genetic background to exercise training responses. Eight-week old male mice from 24 inbred strains (n = 4–10/strain) performed a graded exercise test before and after 4 weeks of exercise training. Before training, exercise capacity was significantly different between strains when expressed as time (range = 21–42 min) and work performed (range = 0.42–3.89 kg·m). The responses to training also were significantly different between strains, ranging from a decrease of 2.2 min in NON/ShiLtJ mice to an increase of 8.7 min in SWR/J mice. Changes in work also varied considerably between the lowest (−0.24 kg·m in NON/ShiLtJ) and highest (+2.30 kg·m in FVB/NJ) performing strains. Heart and skeletal muscle masses also varied significantly between strains. Two broad sense heritability estimates were calculated for each measure of exercise capacity and for responses to training. For change in run time, the intraclass correlation between mice within the same inbred strain (rI) was 0.58 and the coefficient of genetic determination (g2) was 0.41. Heritability estimates were similar for the change in work: rI = 0.54 and g2 = 0.37. In conclusion, these results indicate genetic background significantly influences responses to exercise training.

Cytotoxic T-cells mediate exercise-induced reductions in tumor growth

“…To address the role of immunity on the effects of exercise in neoplasia, we first assessed how repeated voluntary exertion influenced tumor progression in mice, using a genetic model of mammary cancer induced by the MMTV-PyMT transgene on the FVB inbred strain background ( Figure 1—figure supplement 1A ). FVB inbred mice are enthusiastic runners relative to most other inbred strains ( Avila et al, 2017 ), and the MMTV-PyMT model in many regard mimics the gradual progression of human breast cancer ( Lin et al, 2003 ). PyMT+ mice ran on average 6 km/day ( Figure 1—figure supplement 1B ).…”

Cardiorespiratory fitness predicts effective connectivity between the hippocampus and default mode network nodes in young adults

“…Converging evidence from animal and human studies can be challenging given that CRF is rarely measured in rodents (e.g., see Wisløff et al, ) and cellular‐level changes, such as adult hippocampal neurogenesis, cannot yet be directly measured in living humans. One parallel between these two bodies of literature is that CRF is increased through aerobic exercise training in both rodents (Avila, Kim, & Massett, ; Bedford et al, ; Lambert & Noakes, ; Teixeira‐Coelho et al, ) and humans (Hagberg et al, ; Kohrt et al, ). This may suggest that in rodents, greater CRF may be the underlying factor responsible for the relationship between aerobic exercise and adult hippocampal neurogenesis, hippocampal vasculature, and HC‐dependent memory task performance.…”

Mitochondrial DNA lesions and copy number are strain dependent in endurance‐trained mice

“…The mouse tissue samples (plantaris skeletal muscle) analyzed in this study were taken from previously published work by Avila et al (2017). The protocols used in the study by Avila et al (2017) conformed to the standards of humane animal care and were approved by the Texas A&M University Institutional Animal Care and Use Committee (AUPs 2010-245 and 2013-0223). The present work for this investigation included a total of 37 six to seven-week-old male mice were purchased from Jackson Laboratory (Bar Harbor, ME) and allowed at least 1 week to acclimatize to their new environment.…”