Architecture of energy balance traits in emerging lines of the Collaborative Cross

Abstract

The potential utility of the Collaborative Cross (CC) mouse resource was evaluated to better understand complex traits related to energy balance. A primary focus was to examine if genetic diversity in emerging CC lines (pre-CC) would translate into equivalent phenotypic diversity. Second, we mapped quantitative trait loci (QTL) for 15 metabolism- and exercise-related phenotypes in this population. We evaluated metabolic and voluntary exercise traits in 176 pre-CC lines, revealing phenotypic variation often exceeding that seen across the eight founder strains from which the pre-CC was derived. Many phenotypic correlations existing within the founder strains were no longer significant in the pre-CC population, potentially representing reduced linkage disequilibrium (LD) of regions harboring multiple genes with effects on energy balance or disruption of genetic structure of extant inbred strains with substantial shared ancestry. QTL mapping revealed five significant and eight suggestive QTL for body weight (Chr 4, 7.54 Mb; CI 3.32-10.34 Mb; Bwq14), body composition, wheel running (Chr 16, 33.2 Mb; CI 32.5-38.3 Mb), body weight change in response to exercise (1: Chr 6, 77.7Mb; CI 72.2-83.4 Mb and 2: Chr 6, 42.8 Mb; CI 39.4-48.1 Mb), and food intake during exercise (Chr 12, 85.1 Mb; CI 82.9-89.0 Mb). Some QTL overlapped with previously mapped QTL for similar traits, whereas other QTL appear to represent novel loci. These results suggest that the CC will be a powerful, high-precision tool for examining the genetic architecture of complex traits such as those involved in regulation of energy balance.

Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity

“…Body composition was measured in live mice without anesthesia by quantitative magnetic resonance using an EchoMRI-100 whole body composition analyzer (EchoMRI, Houston, TX), as described ( 28 ). Fat and lean mass were quantifi ed at baseline, week 2 and week 4, and expressed as a percentage of total body weight.…”

“…Fat and lean mass were quantifi ed at baseline, week 2 and week 4, and expressed as a percentage of total body weight. At week 3, oxygen consumption (VO 2 ) and carbon dioxide production (VCO 2 ) were quantifi ed by indirect calorimetry in unrestrained individually housed mice using a TSE LabMaster system (TSE Systems, Chesterfi eld, MO), which also quantifi es food and water consumption ( 28 ). Measurements were obtained in 27 min intervals over 24 h, normalized to total body weight, and averaged.…”

The need for mouse models in osteoporosis genetics research

“…37 Although the wild-derived CAST / EiJ strain has been used in two separate studies for BMD QTL mapping, 20 the WSB / EiJ strain, which is M. m. domesticus , and PWD / PhJ strain, which is essentially pure M. m. musculus , 37 have not been used extensively in skeletal biology. The increase in genetic diversity seen in the CC may in part explain the number of novel QTL mapped for energy expenditure, 33 and bodes well for BMD studies.…”

“…Thus, five candidate genes for a QTL is nearly 2 orders of magnitude improvement in resolution. The power to map QTL utilizing the pre-CC is diminished relative to what is predicted for the completed lines 33 and accordingly, there are high expectations for the final strains.…”

LeCollaborative Cross

“…• Des lignées du pré-CC ont également été analysées pour plusieurs dizaines d'autres caractères qui concernent le niveau d'expression des ARNm (eQTL), la reproduction, le comportement, la morphologie, la physiologie et la composition de la microflore intestinale [30][31][32]. Ces études montrent que malgré les conséquences inévitables de la mise à l'état homozygote dans un environnement contrôlé bien différent du milieu naturel, il subsiste entre les lignées CC des phénotypes suffisamment contrastés pour permettre une cartographie fine en utilisant un échantillon d'animaux d'une taille raisonnable.…”