Previous genetic association studies of physical activity, in both animal and human models, have been limited in number of subjects and genetically homozygous strains used as well as number of genomic markers available for analysis. Expansion of the available mouse physical activity strain screens and the recently published dense single-nucleotide polymorphism (SNP) map of the mouse genome (≈8.3 million SNPs) and associated statistical methods allowed us to construct a more generalizable map of the quantitative trait loci (QTL) associated with physical activity. Specifically, we measured wheel running activity in male and female mice (average age 9 wk) in 41 inbred strains and used activity data from 38 of these strains in a haplotype association mapping analysis to determine QTL associated with activity. As seen previously, there was a large range of activity patterns among the strains, with the highest and lowest strains differing significantly in daily distance run (27.4-fold), duration of activity (23.6-fold), and speed (2.9-fold). On a daily basis, female mice ran further (24%), longer (13%), and faster (11%). Twelve QTL were identified, with three (on Chr. 12, 18, and 19) in both male and female mice, five specific to males, and four specific to females. Eight of the 12 QTL, including the 3 general QTL found for both sexes, fell into intergenic areas. The results of this study further support the findings of a moderate to high heritability of physical activity and add general genomic areas applicable to a large number of mouse strains that can be further mined for candidate genes associated with regulation of physical activity. Additionally, results suggest that potential genetic mechanisms arising from traditional noncoding regions of the genome may be involved in regulation of physical activity.

Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been...

Automobile racing is one of the largest spectator sports in the world with male and female drivers competing together. Popular media has speculated on the relative capabilities of males and females in automobile racing, yet there are no scientific investigations examining physiological responses to racing among males and females.Purpose: 1) To evaluate the physiological responses of male and female drivers in open and closed cockpit race cars, 2) to examine the moderating influence of menstrual cycle phase on physiological responses to racing among female drivers.Methods: HR, breathing rate, skin temperature, core temperature, and Physiological Strain Index (PSI) were measured using the Equivital Life Monitor in male (n= 6) and female (n= 6) drivers at three races in open or closed cockpit cars. Among females, menstrual cycle phase for each race was recorded.Results: During racing conditions there was no difference (P> 0.05) between male and female drivers for HR, skin temperature, core temperature, or PSI. The female drivers had a higher (P< 0.001) breathing rate compared with the male drivers. Compared with the follicular phase, the luteal phase had an increased (P< 0.001) HR, breathing rate, skin temperature, core temperature, and PSI. The closed cockpit cars elicited (P< 0.001) a higher skin temperature, core temperature and PSI as compared with the open cockpit cars.Conclusions: There were no differences in the physiological responses to automobile racing between male and female drivers. The luteal phase elicited higher physiological responses than the follicular phase, but was not different from the male drivers. Thereby, practitioners should focus on reducing stresses induced by a closed cockpit race car as opposed to the menstrual cycle.

Physical activity is associated with disease prevention and overall wellbeing. Additionally there has been evidence that physical activity level is a result of genetic influence. However, there has not been a reliable method to silence candidate genes in vivo to determine causal mechanisms of physical activity regulation. Vivo-morpholinos are a potential method to transiently silence specific genes. Thus, the aim of this study was to validate the use of Vivo-morpholinos in a mouse model for voluntary physical activity with several sub-objectives. We observed that Vivo-morpholinos achieved between 60–97% knockdown of Drd1-, Vmat2-, and Glut4-protein in skeletal muscle, the delivery moiety of Vivo-morpholinos (scramble) did not influence physical activity and that a cocktail of multiple Vivo-morpholinos can be given in a single treatment to achieve protein knockdown of two different targeted proteins in skeletal muscle simultaneously. Knocking down Drd1, Vmat2, or Glut4 protein in skeletal muscle did not affect physical activity. Vivo-morpholinos injected intravenously alone did not significantly knockdown Vmat2-protein expression in the brain (p = 0.28). However, the use of a bradykinin analog to increase blood-brain-barrier permeability in conjunction with the Vivo-morpholinos significantly (p = 0.0001) decreased Vmat2-protein in the brain with a corresponding later over-expression of Vmat2 coincident with a significant (p = 0.0016) increase in physical activity. We conclude that Vivo-morpholinos can be a valuable tool in determining causal gene-phenotype relationships in whole animal models.