Parent-of-origin effects on voluntary exercise levels and body composition in mice

Abstract

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♀ × 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.

Maternal over-nutrition and offspring obesity predisposition: targets for preventative interventions

“…57 Voluntary wheel cage running activity of mice has been shown to have strong parent-of-origin effects. 58 In this study, mice born to a breeding cross between mothers of a selectively bred high activity strain and fathers of the wildtype C57BL/6J displayed significantly more activity than offspring of a reciprocal progenitor cross of wild-type mothers and high-activity fathers. Indeed in humans, chromosomal loci influencing activity levels have been known for some time.…”

Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors

“…A moderately (G 4 ) advanced intercross line (AIL) was bred from reciprocal crosses between the inbred strain C57BL/6J and the ICR-derived HR line (54). In brief, F 3 breeding pairs produced multiple litters to expand (n = 815) the G 4 population, with staggered mating to reduce intergroup age variation.…”

Functional Genomic Architecture of Predisposition to Voluntary Exercise in Mice: Expression QTL in the Brain

“…Among 100 randomly selected, statistically significant, trans-acting eQTL the average size of the 95% C.I. (defined by one LOD drop) was 15.9 Mb Figure 1 The number of statistically significant (P # 0.05, adjusted for multiple comparisons) partial correlations, adjusted for sex and parent of origin, factors with known phenotypic effects (see Kelly et al 2010a) between 17,571 significantly expressed transcripts, and exercise and body composition-related phenotypes. In total, 36 exercise-related phenotypes and 17 traits related to food consumption, body weight and composition, and change in body weight and composition as a result of 6 days of voluntary exercise on wheels were observed.…”

“…Details regarding the creation and phenotyping of the G 4 population have been described elsewhere (Kelly et al 2010a). Only methodological details relevant to the current suite of phenotypes and the corresponding statistical analyses will be described here.…”

“…The AIL was created through reciprocal crosses between a line selectively bred for high voluntary wheel running and the inbred strain C57BL/6J (Kelly et al 2010a). The use of an AIL (as opposed to an F 2 population) resulted in a threefold expansion of the genetic map (Kelly et al 2010b) and led to increased QTL mapping resolution with reduced confidence intervals (C.I.…”