Abstract
Functional genome analysis usually is performed on the level of genotype–phenotype interaction. However, phenotypes also depend on the relations between genomes and environment. In our experimental system, we observed differential response to environmental factors defined by different conditions of husbandry in a semi-barrier unit or in a SPF (specific pathogen free) barrier unit, which resulted in partial reversal of phenotypes previously observed under semi-barrier conditions. To provide an update of basic phenotypes in unselected and randomly mated controls (DUC) and long-term selected DUhTP (Dummerstorf high treadmill performance) mice in the SPF facility, we compared growth parameters, reproductive performance, the accretion of muscle and fat mass, physical activity, and running performance as well as food intake in all experimental groups. For selected parameters, the comparative analysis spans more than 30 generations. In DUC mice, under SPF conditions a more than threefold (P < 0.0001) higher subcutaneous fat mass, higher muscle mass by about 25% (P < 0.0001), but lower epididymal fat mass in DUhTP mice by about 20% (P < 0.0001) were observed. In SPF husbandry, body weight increased to a stronger extent in adult DUC mice (≈ 20%; P < 0.0001) than in DUhTP mice (≈ 8%; P = 0.001). The concentrations of IGF-1 and IGFBPs in the serum as well as the liver weights were similar in all experimental groups, indicating growth effects independent of the somatotropic axis. Under SPF conditions the litter size at birth increased in DUC mice (P < 0.001) but not in DUhTP mice. The differential effect of husbandry on body weights at day 21 and concentrations of triglycerides in the serum of our model were due to the different diets used in the semi-barrier and in the SPF facility. Our results demonstrate differential trait response to environmental factors resulting in partial phenotype conversion in our experimental system. The existence of conditional phenotypes as a result of genotype–environment interactions points to the importance of environmental factors in functional genome analysis.
Highlights
Since 1983 in Dummerstorf a high treadmill performance mouse model (DUhTP) had been established for the analysis of energy metabolism applying long term phenotype selection for high treadmill performance (Dietl et al 2004)
In 2012, all mouse lines were transferred from the semi-barrier unit to the newly built mouse facility with standardized environmental and working procedures defined by the SPF status
At an age of 42 days, DUCSPF mice were characterized by elevated body mass if compared to DUC mice kept in the semi-barrier (+ 18%; P < 0.0001; Fig. 1b)
Summary
Since 1983 in Dummerstorf a high treadmill performance mouse model (DUhTP) had been established for the analysis of energy metabolism applying long term phenotype selection for high treadmill performance (Dietl et al 2004). Journal of Comparative Physiology B (2018) 188:527–539 et al 2000) Both the unselected and randomly mated control line (DUC) and the DUhTP originate from this genetic founder pool. DUhTP mice cover fourfold increased distances if compared to DUC mice (Brenmoehl et al 2013). In response to moderate voluntary physical activity over a period of 3 weeks in running wheels, concentrations of inducer of mitochondrial biogenesis are further increased resulting in efficient fat mobilization in DUhTP mice (Brenmoehl et al 2015). We identified genetic linkage of fat cell browning and metabolic health, because young male DUhTP mice are characterized by increased tolerance against oral glucose (Brenmoehl et al 2016). Sedentary DUhTP mice are characterized by increased accumulation of body fat compared to DUC mice (Brenmoehl et al 2015). Because we used different diets in the semi-barrier and in the SPF facility, we assessed the effects of both commercial diets on body weight under identical husbandry conditions
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