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Articles by D. L Nehrenberg
Total Records ( 3 ) for D. L Nehrenberg
  D. L Nehrenberg , S Wang , R. M Hannon , T Garland and D. Pomp
 

Exercise improves many aspects of human health, yet many people remain inactive even when exercise is prescribed. We previously created a backcross (BC) between mice selectively bred for high levels of voluntary wheel running (VWR) and fixed for "mini muscle" (MM), a recessive mutation causing ~50% reduction in triceps surae mass. We previously showed that BC mice having the MM trait ran faster and further than mice without MM and that MM maps to chromosome 11. Here, we genotyped the BC with genome-wide single nucleotide polymorphisms to identify quantitative trait loci (QTL) controlling voluntary exercise and tissue and body mass traits and to determine whether these QTL interact with the MM locus or with sex. We detected 3 VWR QTL, representing the first voluntary exercise QTL mapped using this high running selection line, and 5 tissue mass QTL. Several interactions between trait QTL and the MM locus as well as sex were also identified. These results begin to explain the genetic architecture of VWR and further support MM as a locus having major effects, including its main effects on the muscle phenotype, its pleiotropic effects on wheel running and tissue mass traits, and through its interactions with other QTL and with sex.

  S. A Kelly , D. L Nehrenberg , K Hua , R. R Gordon , T Garland and D. Pomp
 

Despite the health-related benefits of exercise, many people do not engage in enough activity to realize the rewards, and little is known regarding the genetic or environmental components that account for this individual variation. We created and phenotyped a large G4 advanced intercross line originating from reciprocal crosses between mice with genetic propensity for increased voluntary exercise (HR line) and the inbred strain C57BL/6J. G4 females (compared to males) ran significantly more when provided access to a running wheel and were smaller with a greater percentage of body fat pre- and postwheel access. Change in body composition resulting from a 6-day exposure to wheels varied between the sexes with females generally regulating energy balance more precisely in the presence of exercise. We observed parent-of-origin effects on most voluntary wheel running and body composition traits, which accounted for 3–13% of the total phenotypic variance pooled across sexes. G4 individuals descended from progenitor (F0) crosses of HR and C57BL/6J ran greater distances, spent more time running, ran at higher maximum speeds/day, and had lower percent body fat and higher percent lean mass than mice descended from reciprocal progenitor crosses (C57BL/6J x HR). For some traits, significant interactions between parent of origin and sex were observed. We discuss these results in the context of sex dependent activity and weight loss patterns, the contribution of parent-of-origin effects to predisposition for voluntary exercise, and the genetic (i.e., X-linked or mtDNA variations), epigenetic (i.e., genomic imprinting), and environmental (i.e., in utero environment or maternal care) phenomena potentially modulating these effects.

  S. A Kelly , D. L Nehrenberg , J. L Peirce , K Hua , B. M Steffy , T Wiltshire , F Pardo Manuel de Villena , T Garland and D. Pomp
 

Exercise is essential for health, yet the amount, duration, and intensity that individuals engage in are strikingly variable, even under prescription. Our focus was to identify the locations and effects of quantitative trait loci (QTL) controlling genetic predisposition for exercise-related traits, utilizing a large advanced intercross line (AIL) of mice. This AIL (G4) population originated from a reciprocal cross between mice with genetic propensity for increased voluntary exercise [high-runner (HR) line, selectively bred for increased wheel running] and the inbred strain C57BL/6J. After adjusting for family structure, we detected 32 significant and 13 suggestive QTL representing both daily running traits (distance, duration, average speed, and maximum speed) and the mean of these traits on days 5 and 6 (the selection criteria for HR) of a 6-day test conducted at 8 wk of age, with many colocalizing to similar genomic regions. Additionally, seven significant and five suggestive QTL were observed for the slope and intercept of a linear regression across all 6 days of running, some representing a combination of the daily traits. We also observed two significant and two suggestive QTL for body mass before exercise. These results, from a well-defined animal model, reinforce a genetic basis for the predisposition to engage in voluntary exercise, dissect this predisposition into daily segments across a continuous time period, and present unique QTL that may provide insight into the initiation, continuation, and temporal pattern of voluntary activity in mammals.

 
 
 
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