Architecture of energy balance traits in emerging lines of the Collaborative Cross – 15 metabolism- and exercise-related phenotypes


The Collaborative Cross (CC) recombinant inbred panel was conceived as an improved resource for mammalian systems genetics and to overcome many of the limitations of traditional QTL mapping populations. To investigate the utility and insights that can be learned from the CC, experiments were performed involving incipient CC lines that had undergone at least five generations of inbreeding (pre-CC). Pre-CC lines were involved in four distinct phenotyping arms, then genotyped on a high-density Affymetrix platform. In this study, we characterized phenotypic variation and mapped QTL in the pre-CC population for a suite of traits revolving around energy balance, including body weight and body composition both before and after a 12-day period of voluntary exercise in running wheels.


Architecture of energy balance traits in emerging lines of the Collaborative Cross
Mathes WF, Aylor DL, Miller DR, Churchill GA, Chesler EJ, de Villena FP, Threadgill DW, Pomp D.
Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1124-34. PMCID: PMC3118585 [Available on 2012/6/1]




Mice were weaned at ORNL and transferred to a phenotyping facility at the University of North Carolina - Chapel Hill. One hundred and eighty-four lines ranging from generation G2:F5-G2:F12 were transferred to the phenotyping facility and adult male mice, 10-12 weeks of age, from 176 preCC lines were included in the final analyses.

Definitions of phenotypes measured:

  • Body composition prior to start of wheel running (bf_pre) and after the twelve-day wheel trial (bf_post)
  • Body weight at beginning of sedantary phase (bw_pre) and at end of wheel runing phase (bw_post)
  • Change in body weigth (bodyweight_net) and body composition (bodyfat_net) in response to exercise
  • Running distances (run_dist1) and speeds (run_speed1) directly extracted for day 1 of wheel access
  • Running distances (run_dist56) and speeds (run_speed56) averaged for days 5 and 6 of wheel access
  • Running distances (run_dist12) and speeds (run_speed12) averaged for days 11 and 12 of wheel access
  • Nocturnal respiratory exchange ratio, an indicator of energy utilization, measured prior to exercise (nocturnalRER_pre)
  • Food intake when sedentary (FI_Sed).
  • Food intake corrected by body weight during wheel running (FI_RunaveBW) and when sedentary (FI_SedperBW)
  • Wheelfreeness, a measure of performance differences between running wheels

File of phenotypes: exercise_pheno.txt


Each mouse in the pre-CC experiment was genotyped using a highdensity SNP array. Most of the genotyping was completed using ‘‘test’’ arrays. These arrays were developed as an intermediate step in the process of developing the Mouse Diversity array (Yang et al. 2009). There are two versions of the test array: A-array and B-array. The A-array includes 294,878 SNP assays, and the B-array contains 287,687 additional SNP assays. We determined that 181,752 (A-array) and 180,976 (B-array) SNP assays performed well and targeted loci that are polymorphic among the eight founder strains. There is no overlap between the two arrays, but the genome coverage is complete and uniformly distributed in both. In some cases, animals from the same phenotyping arm were genotyped with different arrays. Integration was achieved by merging the two sets and using an HMM to impute haplotypes at loci with missing genotypes. Due to the high marker density, this procedure was very effective. The exercise behavior and metabolism arm was completely genotyped with the A-array. Genotype data is publically available for download at the CC Status website (

Array genotyping data: metabolism filtered genotypes

Processed genotype data: seg_cache_happy_005.tar.gz

Note: Within each csv file you will observe a header for each column of genotypes. The first few link the corresponding mouse strain to a letter - such as the letter A to the strain A/J - and so forth, until the letter H. The following columns correspond to crosses. Their headers are given as sequences of letters, such as ECBDAHFG, ADFEHGBC, and BCGDFEAH. The gender order within these sequences is FMFMFMFM where F = female and M = male. The Y chromosome comes from the last position, mitochondria from the first.