scholarly journals Mean-Variance QTL Mapping Identifies Novel QTL for Circadian Activity and Exploratory Behavior in Mice

2018 ◽  
Author(s):  
Robert W. Corty ◽  
Vivek Kumar ◽  
Lisa M. Tarantino ◽  
Joseph S. Takahashi ◽  
William Valdar
Keyword(s):  
Qtl Mapping ◽  
Linear Model ◽  
Wheel Running ◽  
Interval Mapping ◽  
Residual Variance ◽  
Running Activity ◽  
First Case ◽  
Wheel Running Activity ◽  
Mean Variance

ABSTRACTWe illustrate, through two case studies, that “mean-variance QTL mapping” can discover QTL that traditional interval mapping cannot. Mean-variance QTL mapping is based on the double generalized linear model, which elaborates on the standard linear model by incorporating not only a linear model for the data itself, but also a linear model for the residual variance. Its potential for use in QTL mapping has been described previously, but it remains underutilized, with certain key advantages undemonstrated until now. In the first case study, we use mean-variance QTL mapping to reanalyze a reduced complexity intercross of C57BL/6J and C57BL/6N mice examining circadian behavior and find a mean-controlling QTL for circadian wheel running activity that was not detected by traditional interval mapping. Mean-variance QTL mapping was more powerful than traditional interval mapping at the QTL because it accounted for the fact that mice homozygous for the C57BL/6N allele had less residual variance than the other mice. In the second case study, we reanalyze an intercross between C57BL/6J and C58/J mice examining anxiety-like behaviors, and identify a variance-controlling QTL for rearing behavior. This QTL was not identified in the original analysis because traditional interval mapping does not target variance QTL.

Differential effects of food restriction on pituitary-testicular function in mice

1985 ◽  
Vol 248 (2) ◽  
pp. R181-R189 ◽  
Author(s):  
J. L. Blank ◽  
C. Desjardins
Keyword(s):  
Food Intake ◽  
Animal Models ◽  
Food Restriction ◽  
Wheel Running ◽  
Temporal Organization ◽  
Deer Mice ◽  
House Mice ◽  
Testicular Function ◽  
Running Activity ◽  
Wheel Running Activity

The reproductive responses of two species of wild rodents, house mice and deer mice, were evaluated following a 30% reduction in food intake for 5 wk. These animal models were chosen as prototypes of other rodent species because each employs unique functional adjustments when confronted with reduced resources in their natural habitats. Modest inanition failed to alter pituitary-testicular function in house mice; neither spermatogenesis nor plasma concentrations of luteinizing hormone (LH) and testosterone were modified. In sharp distinction, deer mice exposed to restricted food intake showed significant reductions in plasma LH and testosterone and an accompanying loss in spermatogenesis. Reduced food intake also caused pronounced shifts in the temporal organization and amount of wheel-running activity in both animal models, albeit in a dichotomous fashion. House mice exhibited the same amount of wheel-running activity throughout inanition, but the diel periodicity of locomotor behavior was shifted from the dark to the light period. Deer mice, in comparison, significantly curtailed wheel-running activity during the dark hours but ran in precise phase relationship with the light-dark cycle. Taken together, our results establish that the male reproductive system and its supporting neuroendocrine and behavioral correlates can be disrupted by modest levels of food restriction in certain animal models.

Genetic analysis of daily physical activity using a mouse chromosome substitution strain

2009 ◽  
Vol 39 (1) ◽  
pp. 47-55 ◽  
Author(s):  
He S. Yang ◽  
Martha H. Vitaterna ◽  
Aaron D. Laposky ◽  
Kazuhiro Shimomura ◽  
Fred W. Turek
Keyword(s):  
Physical Activity ◽  
Physical Activity Level ◽  
Wheel Running ◽  
Daily Physical Activity ◽  
Activity Level ◽  
Constant Darkness ◽  
Circadian Period ◽  
Chromosome 13 ◽  
Running Activity ◽  
Wheel Running Activity

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.

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 ◽  
...  
Keyword(s):  
Physical Activity ◽  
Association Mapping ◽  
Wheel Running ◽  
Association Studies ◽  
Mouse Strains ◽  
Haplotype Association ◽  
Male And Female ◽  
Female Mice ◽  
Running Activity ◽  
Wheel Running Activity

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.

Interstrain differences in activity pattern, pineal function, and SCN melatonin receptor density of rats

1999 ◽  
Vol 276 (4) ◽  
pp. R1078-R1086 ◽  
Author(s):  
Gabriela Klante ◽  
Karin Secci ◽  
Mireille Masson-Pévet ◽  
Paul Pévet ◽  
Berthe Vivien-Roels ◽  
...  
Keyword(s):  
Wheel Running ◽  
Activity Patterns ◽  
Temporal Organization ◽  
Receptor Density ◽  
Melatonin Receptor ◽  
Time Pattern ◽  
Melatonin Synthesis ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Inbred Rat

We investigated the possibility that strain-dependent differences in the diurnal pattern of wheel running activity rhythms are also reflected in the melatonin profiles. The inbred rat strains ACI/Ztm, BH/Ztm, and LEW/Ztm. LEW were examined for diurnal [12:12-h light-dark (LD)] wheel running activity, urinary 6-sulphatoxymelatonin (aMT6s) excretion, melatonin concentrations of plasma and pineal glands, and melatonin receptor density in the suprachiasmatic nuclei (SCN). ACI rats displayed unimodal activity patterns with a high level of activity, whereas BH and LEW rats showed multimodal activity patterns with ultradian components and reduced activity levels. In contrast, the individual daily profiles of aMT6s excretion and mean melatonin synthesis followed a unimodal time pattern in all three strains, suggesting that different output pathways of the SCN are responsible for the temporal organization of locomotor activity and pineal melatonin synthesis. In addition, melatonin synthesis at night and SCN melatonin receptor density at day were significantly higher in BH and LEW rats than in ACI rats. These results support the hypothesis of a long-term stimulating effect of melatonin on its own receptor density in the SCN.

scholarly journals Stochastic Modeling of Chemical Compounds in a Limestone Deposit by Unlocking the Complexity in Bivariate Relationships

Minerals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 683 ◽  
Author(s):  
Battalgazy ◽  
Madani
Keyword(s):  
Mineral Resource ◽  
Linear Model ◽  
Stochastic Modeling ◽  
Cross Correlation ◽  
Projection Pursuit ◽  
Chemical Compounds ◽  
Spatial Dependency ◽  
Mean Variance ◽  
Mineral Resource Evaluation

Modeling multivariate variables with complexity in a cross-correlation structure is always applicable to mineral resource evaluation and exploration in multi-element deposits. However, the geostatistical algorithm for such modeling is usually challenging. In this respect, projection pursuit multivariate transform (PPMT), which can successfully handle the complexity of interest in bivariate relationships, may be particularly useful. This work presents an algorithm for combining projection pursuit multivariate transform (PPMT) with a conventional (co)-simulation technique where spatial dependency among variables can be defined by a linear model of co-regionalization (LMC). This algorithm is examined by one real case study in a limestone deposit in the south of Kazakhstan, in which four chemical compounds (CaO, Al2O3, Fe2O3, and SiO2) with complexity in bivariate relationships are analyzed and 100 realizations are produced for each variable. To show the effectiveness of the proposed algorithm, the outputs (realizations) are statistically examined and the results show that this methodology is legitimate for reproduction of original mean, variance, and complex cross-correlation among the variables and can be employed for further processes. Then, the applicability of the concept is demonstrated on a workflow to classify this limestone deposit as measured, indicated, or inferred based on Joint Ore Reserves Committee (JORC) code. The categorization is carried out based on two zone definitions, geological, and mining units.

scholarly journals Acute Exposure to a High-Fat High-Sugar Diet Alters Wheel Running Activity

2018 ◽  
Vol 50 (5S) ◽  
pp. 821
Author(s):  
Katherine A. Stiegel ◽  
Ayland C. Letsinger ◽  
Jorge Z. Granados ◽  
Cedric Cerda ◽  
J. Timothy Lightfoot
Keyword(s):  
Wheel Running ◽  
Acute Exposure ◽  
High Fat ◽  
High Sugar ◽  
Running Activity ◽  
Wheel Running Activity
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