scholarly journals Strain screen and haplotype association mapping of wheel running in inbred mouse strains

2010 ◽  
Vol 109 (3) ◽  
pp. 623-634 ◽  
Author(s):  
J. Timothy Lightfoot ◽  
Larry Leamy ◽  
Daniel Pomp ◽  
Michael J. Turner ◽  
Anthony A. Fodor ◽  
...  

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.

2009 ◽  
Vol 39 (1) ◽  
pp. 47-55 ◽  
Author(s):  
He S. Yang ◽  
Martha H. Vitaterna ◽  
Aaron D. Laposky ◽  
Kazuhiro Shimomura ◽  
Fred W. Turek

There is considerable evidence for a genetic basis underlying individual differences in spontaneous physical activity in humans and animals. Previous publications indicate that the physical activity level and pattern vary among inbred strains of mice and identified a genomic region on chromosome 13 as quantitative trait loci (QTL) for physical activity. To confirm and further characterize the role of chromosome 13 in regulating daily physical activity level and pattern, we conducted a comprehensive phenotypic study in the chromosome 13 substitution strain (CSS-13) in which the individual chromosome 13 from the A/J strain was substituted into an otherwise complete C57BL/6J (B6) genome. The B6 and A/J parental strains exhibited pronounced differences in daily physical activity, sleep-wake structure, circadian period and body weight. Here we report that a single A/J chromosome 13 in the context of a B6 genetic background conferred a profound reduction in both total cage activity and wheel-running activity under a 14:10-h light-dark cycle, as well as in constant darkness, compared with B6 controls. Additionally, CSS-13 mice differed from B6 controls in the diurnal distribution of activity and the day-to-day variability in activity onset. We further performed a linkage analysis and mapped a significant QTL on chromosome 13 regulating the daily wheel running activity level in mice. Taken together, our findings indicate a QTL on chromosome 13 with dramatic and specific effects on daily voluntary physical activity, but not on circadian period, sleep, or other aspects of activity that are different between B6 and A/J strains.


2010 ◽  
Vol 20 ◽  
pp. S284
Author(s):  
M. Ágoston ◽  
J. Wellmann ◽  
P. Delagrange ◽  
M. Spedding ◽  
I. Gacsályi ◽  
...  

2004 ◽  
Vol 19 (3) ◽  
pp. 270-276 ◽  
Author(s):  
J. Timothy Lightfoot ◽  
Michael J. Turner ◽  
Meredith Daves ◽  
Anna Vordermark ◽  
Steven R. Kleeberger

This project was designed to determine the genetic (between-strain) and environmental (within-strain) variance in daily running wheel activity level in inbred mice. Five male and five female mice, 9.7–15.3 wk old, from each of 13 strains (A/J, AKR/J, BALB/cJ, C3H/HeJ, C57Bl/6J, C57L/J, C3Heb/FeJ, CBA/J, DBA/2J, SWR/J, MRL/MpJ, SPRET/Ei, and CAST/Ei) as well as five female NZB/BinJ mice were housed individually. A running wheel in each cage was interfaced with a magnetic sensor to measure total daily distance and exercise time for each animal every 24 h for 21 consecutive days (3 wk). Average daily distance (km), duration (min), and velocity (m/min) for each strain was then calculated. Significant interstrain differences in average daily distance ( P < 0.001), average daily exercise duration ( P < 0.0001), and average daily exercise velocity ( P < 0.0001) were found, with C57L/J mice running farther and faster than the other strains. Sex was a significant factor in daily running wheel activity, with female mice running an average of 20% farther ( P = 0.01) and 38% faster ( P < 0.0001) than male mice. The male mice ran 15% longer duration on a daily basis ( P = 0.0091). Weight was only associated with exercise velocity in the female mice, but this relationship was not significant when subdivided by strain. Broad-sense heritability estimates on the physical activity differed by sex (for distance, male 31–48% and female 12–22%; for duration, male 44–61% and female 12–21%; for velocity, male 49–66% and female 44–61%). In conclusion, these data indicate that daily running wheel activity level in mice is significantly affected by genetic background and sex.


2017 ◽  
Vol 2 (105) ◽  
pp. 14-19
Author(s):  
Andrej Fokin ◽  
Petras Minderis ◽  
Rasa Žūkienė ◽  
Aivaras Ratkevičius

Background.  Citrate  synthase  (CS)  plays  an  important  role  in  the  regulation  of  carbohydrate  oxidation. Variation in citrate synthase activity has an influence on metabolic changes. We tested the hypothesis that reduced mitochondrial CS activity could affect energy expenditure (EE) and respiratory quotient (RQ) in mouse model with an emphasizing on gender differences between tested strains. Methods. 16-week of age wild-type C57Bl/6J (B6) mouse strain, B6.A-(rs3676616-D10Utsw1)/Kjn (B6.A) and C57BL/6J-Chr 10A/J/NaJ (B6.A10) strains with reduced CS activity were studied in physiocage by the “Panlab” metabolism analysing equipment. The following parameters were calculated: EE (ml/min/kg^0.75), RQ, physical activity and rearing. Results. In female mice EE values were lower in B6.A10 strain compared to wild-type B6 strain. RQ values were similar in all tested mouse strains. In B6 mice EE was higher in females compared to males. Rearing was elevated in females of B6 mice compared to males. Conclusions. EE was lower in B6.A10 compared to B6 mice. Gender differences were noticed only in B6 mice: EE and rearing were significantly higher in female compared to male mice. Current study did not reveal any other association between reduced CS activity and EE or RQ variation in male and female mice.


2008 ◽  
Vol 2 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Anthony Ferreira ◽  
Fabien Cornilleau ◽  
Fernando Perez-Diaz ◽  
Charles Cohen-Salmon

This study used animal models to examine potential similarities between dependence on physical activity (i.e., exercise) and dependence on morphine. Using C57BL/6 mice, the study also tested the hypothesis that physical exercise (e.g., long-term wheel running) may enhance vulnerability to the development of morphine dependence. The existence of an endorphin-related dependence induced by physical activity was also assessed. Naloxone was used to precipitate morphine withdrawal in mice accustomed to morphine. Specifically, the study sought to assess the intensity of addiction provoked by injection of morphine in mice that engaged in wheel-running activity as opposed to inactive mice. After 25 days of free access to activity wheel, mice that engaged in wheel-running demonstrated increased vulnerability to naloxone-induced withdrawal symptoms, which may be linked to activation of peripheral, as opposed to central, opioid receptors. These results indicate a behavioral interaction in which engaging in wheel running appears to potentiate the effects of morphine addiction. Implications of these findings for understanding human behavior and exercise addiction are also discussed.


2006 ◽  
Vol 290 (3) ◽  
pp. E480-E489 ◽  
Author(s):  
David S. Kump ◽  
Matthew J. Laye ◽  
Frank W. Booth

Triacylglycerol synthesis in rat epididymal fat overshoots sedentary levels at 10, 29, and 53 h of physical inactivity after 21 days of wheel running. The purposes of the present study were to determine 1) whether this effect is also observed after an acute bout of physical activity and 2) what enzymatic changes might contribute to this effect. We show that more than one bout of physical activity, such as that which occurs with 21 days of wheel running, is necessary for palmitic acid incorporation into triacylglyceride (triglyceride synthesis) to overshoot sedentary values, which suggests that pretranslational mechanisms may be responsible for this overshoot effect. Ten hours after 21 days of wheel running, activity of the mitochondrial glycerol-3-phosphate acyltransferase-1 (mtGPAT1) isoform, a key regulator of triacylglycerol synthesis, overshot sedentary values by 48% and remained higher than sedentary values at 29 and 53 h of reduced physical activity. The overshoot in mtGPAT1 activity was accompanied by an increase in mtGPAT protein level. Cyclic AMP response element-binding protein-binding protein level was higher in sedentary 29 h after 21 days of wheel running. AMP kinase-α Thr172 phosphorylation was increased immediately after treadmill running, but decreased to sedentary values by 5 h after activity. Casein kinase-2α protein level and activity were unchanged. We conclude that an increase in mtGPAT protein might contribute to the overshoot in triacylglycerol synthesis.


2013 ◽  
Vol 305 (12) ◽  
pp. R1433-R1440 ◽  
Author(s):  
Stefano Guidotti ◽  
Izabella Jónás ◽  
Kristin A. Schubert ◽  
Theodore Garland ◽  
Harro A. J. Meijer ◽  
...  

Feeding a diet high in fat and sucrose (HFS) during pregnancy and lactation is known to increase susceptibility to develop metabolic derangements later in life. A trait for increased behavioral activity may oppose these effects, since this would drain energy from milk produced to be made available to the offspring. To investigate these interactions, we assessed several components of behavioral energetics during lactation in control mice (C) and in mice of two lines selectively bred for high wheel-running activity (S1, S2) subjected to a HFS diet or a low-fat (LF) diet. Energy intake, litter growth, and milk energy output at peak lactation (MEO; assessed by subtracting maternal metabolic rate from energy intake) were elevated in HFS-feeding dams across all lines compared with the LF condition, an effect that was particularly evident in the S dams. This effect was not preceded by improved lactation behaviors assessed between postnatal days 1 and 7 (PND 1–7). In fact, S1 dams had less high-quality nursing, and S2 dams showed poorer pup retrieval than C dams during PND 1–7, and S dams had generally higher levels of physical activity at peak lactation. These data demonstrate that HFS feeding increases MEO underlying increased litter and pup growth, particularly in mice with a trait for increased behavioral physical activity.


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