Poster 23
Presenter: Arimantas Lionikas
Wednesday, 3:00 – 5:00pm

Dissection of the Genetic Architecture of Musculoskeletal Traits in Collaborative Cross

Stephanie A. Shields¹, Graeme A. Matheson¹, Lois Balmer², Ramesh Ram², Grant Morahan², Arimantas Lionikas^1
1 School of Medical Sciences, University of Aberdeen, Scotland UK; ² Centre for Diabetes Research, Western Australian Institue for Medical Research, and University of Western Australia, Perth WA 6000 Australia

The founder strains of the collaborative cross (CC) differ substantially in body size. Because skeletal muscles and bones are major determinants of body size, we initiated QTL mapping of the weights of five hindlimb muscles: (tibialis anterior (TA), extensor digitorum longus (EDL), gastrocnemius, plantaris and soleus) as well as femur length in 4 founder strains (A/J, 129, NOD/Lt, C57BL/6) and 28 CC strains. Male mice (n 155, between 2 and 13 per strain) aged between 40 and 59 days were phenotyped. HAPPY and DOQTL software were used for QTL mapping. The genetic correlations between the age-adjusted strain means ranged from 0.37 (soleus weight and femur length, p<0.05) to 0.89 (weight of TA and gastrocnemius, p< 1×10^-10). Muscle weight and bone length were lowest in NOD/Lt strain and largest in WAB2_DH (TA, plantaris), C57BL/6 (EDL, gastrocnemiuse and soleus) and BEM_AG (femur) strains. Differences of 2.3- to 3.3-fold were observed between the extremes for muscle weight (ANOVA for strain effect P < 1×10^-13) and 1.4-fold for the femur length (P < 1×10^-8). The most robust QTLs (95% confidence) for muscle weight and femur length mapped to chromosomes 1 and 10, respectively. Chromosomes 1, 2, 3, 4, 6, 8, 13 and 16 also harboured QTLs (90% confidence) affecting various phenotypes. We conclude that the CC provides an excellent model for mapping genes affecting variation in musculoskeletal traits.

Supported by grants: NIAMS AR056280; Marie Curie IRG 249156