Quantitative trait loci for exercise training responses in FVB/NJ and C57BL/6J mice

Abstract

Massett MP, Fan R, Berk BC. Quantitative trait loci for exercise training responses in FVB/NJ and C57BL/6J mice. Physiol Genomics 40: 15-22, 2009. First published September 29, 2009 doi:10.1152/physiolgenomics.00116.2009.-The genetic factors determining the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with adaptation to exercise training in a cross between FVB/NJ (FVB) and C57BL/6J (B6) mice. Mice completed an exercise performance test before and after a 4-wk treadmill running program, and changes in exercise capacity, expressed as work (kg ⅐ m), were calculated. Changes in work in F2 mice averaged 1.51 Ϯ 0.08 kg ⅐ m (94.3 Ϯ 7.3%), with a range of Ϫ1.67 to ϩ4.55 kg ⅐ m. All F2 mice (n ϭ 188) were genotyped at 20-cM intervals with 103 single nucleotide polymorphisms (SNPs), and genomewide linkage scans were performed for pretraining, posttraining, and change in work. Significant QTL for pretraining work were located on chromosomes 14 at 4.0 cM [3.72 logarithm of odds (LOD)] and 19 at 34.4 cM (3.63 LOD). For posttraining work significant QTL were located on chromosomes 3 at 60 cM (4.66 LOD) and 14 at 26 cM (4.99 LOD). Suggestive QTL for changes in work were found on chromosomes 11 at 44.6 cM (2.30 LOD) and 14 at 36 cM (2.25 LOD). When pretraining work was used as a covariate, a potential QTL for change in work was identified on chromosome 6 at 68 cM (3.56 LOD). These data indicate that one or more QTL determine exercise capacity and training responses in mice. Furthermore, these data suggest that the genes that determine pretraining work and training responses may differ. treadmill running; genetic factors LOW EXERCISE CAPACITY or cardiorespiratory fitness is comparable to elevated systolic blood pressure, obesity, diabetes, and smoking as a risk factor and predictor of future disease (33,47). Improving cardiorespiratory fitness through increased physical activity can significantly reduce the risk of all-cause mortality (8), regardless of the level of initial fitness (22). However, there is a high degree of individual variation in the responses to exercise training. For example, there are some individuals who might not show an increase in maximal oxygen consumption (V O 2max ) in response to endurance training (9, 12). Consequently, identifying the genetic factors modulating the adaptations to exercise may provide insight into individual differences in responses to training. However, the genetic factors determining the magnitude of the response to exercise are poorly understood.Initial studies investigating the genetic basis for exercise capacity and training responses focused on familial resemblance and heritability of performance phenotypes. Results from cross-sectional, twin, and prospective studies indicate that the heritability for training-induced changes in V O 2max and submaximal power output ranges from 25% to 50% (11). Heritability estimates from family studies also vary between 25% and 50%, depending...

Divergent physiological characteristics and responses to endurance training among inbred mouse strains

“…Thus, understanding of the mechanisms underlying the between strain differences at baseline could also explain some of the difference in the degree of adaptation to training. This assumption was consistent with observation of an overlap between QTL affecting pre-and post-training endurance in both mice (Massett et al, 2009) and humans (Rico-Sanz et al, 2004).…”

“…Therefore, this relatively small difference in accumulated training time cannot explain the nonresponder strains. Instead, these findings together with the results of the mapping of quantitative trait loci (QTL) support the importance of genetic variation in adaptation to training (Massett et al, 2009). More importantly, our observation indicated that nonresponder strains were also poor performers at the baseline.…”

“…This could help identify new models for studying the mechanisms underlying those traits. Several studies used a forced running paradigm to characterize a number of inbred strains for running capacity (Lightfoot et al., ; Lerman et al., ; Massett & Berk, ; Haramizu et al., ) and reported heritability estimates ranging between 0.47 and 0.73 (Lightfoot et al., , ; Lerman et al., ; Massett et al., ). A systematic exploration of musculo‐skeletal phenotypes, such as the proportion of different fiber types, or the enzymatic activity in muscle, although somewhat limited in terms of the number of screened strains, also revealed substantial strain differences (Van Der Laarse et al., ; Nimmo et al., ; Totsuka et al., ; Ratkevicius et al., ).…”

Forced Running Endurance Is Influenced by Gene(s) on Mouse Chromosome 10

“…The test is a modification of the protocol described earlier (Knab et al, 2009; Massett et al, 2009). The starting speed of the treadmill at a zero incline was set at 16.8 m/min.…”

Exercise Capacity and Response to Training Quantitative Trait Loci in a NZW X 129S1 Intercross and Combined Cross Analysis of Inbred Mouse Strains

“…Based on significant strain differences in baseline or pre-training exercise capacity measured during a graded treadmill test, quantitative trait loci (QTL) for exercise capacity have been identified in rats and mice [ 17 – 21 ]. In addition, a genome wide linkage scan for exercise capacity and responses to training was performed using in an F 2 population derived from inbred FVB/NJ (FVB) and C57BL/6J (B6) mice [ 20 ]. In (FVB x B6) F 2 population, several significant and suggestive QTL for pre- and post-training exercise capacity and the responses to training (i.e., change in exercise capacity) were identified.…”