Partial phenotype conversion and differential trait response to conditions of husbandry in mice

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.

Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse

“…Moreover, our Titan mice showed impaired glucose clearance at 13-14 weeks of age, while Titan mice of generation 146 (under chow diet) showed a non-significant slower glucose clearance at 12 weeks of age ( 11 ). Possible causes for these differences are the further weight increase of Titan mice since generation 146, as well as the changes in diet and housing conditions implemented around generation 153 ( 14 ).…”

“…In 2011/2012, the Titan mouse lines (generations 153 and 154) were transferred into a new state-of-the-art pathogen-free animal facility. Also, the mouse diet composition changed at that time point ( 14 ). These modifications might have impacted some characteristics of the Titan mice, calling for a thorough characterization of the present mouse line.…”

Control of Protein and Energy Metabolism in the Pituitary Gland in Response to Three-Week Running Training in Adult Male Mice

“…Because DUhTP and DUC mice had different running capacities, DUhTP and DUC were trained for 30 and 15 min per day, respectively. These training intensities correspond to 22.6% of the submaximal treadmill running capabilities in both mouse lines, determined in previous generations ( [ 11 ], DUhTP: 2 h 13 min; DUC: 1 h 6 min). At the age of 49 days, the training program started with an initial run by animals of both lines for 15 and 30 min.…”

Analysis of Activity-Dependent Energy Metabolism in Mice Reveals Regulation of Mitochondrial Fission and Fusion mRNA by Voluntary Physical Exercise in Subcutaneous Fat from Male Marathon Mice (DUhTP)

“…This result was different from our previous study in animals of earlier generations under conditions of a semi-barrier animal facility [ 8 , 24 ], where no significant difference of voluntary activity was described in the DUhTP and DUC mice. Meanwhile, the mice were brought to an SPF facility, and several genotype/environment interactions have been identified [ 26 ]. In particular, the new environment had a significant effect on growth and reproduction traits.…”

“…Since the selection was based on a single submaximal run with males after mating, a selection line was generated, exhibiting genetically high running ability without any previous training. Interestingly, the extraordinary endurance performance of the DUhTP animals did not correlate with elevated voluntary running wheel activity, which was not significantly different from the unselected controls (DUC mice) [ 8 , 24 , 26 ]. DUhTP mice have selection-related adaptations that indicate the efficient use of lipids for superior endurance performance.…”