Quantitative trait loci (QTL) for lean body mass and body length in MRL/MPJ and SJL/J F(2) mice.

Studies on the genetic mechanisms involved in the regulation of lean body mass (LBM) in mammals are minimal, although LBM is associated with a competent immune system and an overall good (healthy) body functional status. In this study, we performed a high-density genome-wide scan using 633 (MRL/MPJ x SJL/J) F(2) intercross to identify the quantitative trait loci (QTL) involved in the regulation of LBM. We hypothesized that additional QTL can be identified using a different mouse cross (MRL/SJL cross). Ten QTL were identified for LBM on chromosomes (chrs) 2, 6, 7, 9,13 and 14. Of those ten, QTL on chrs 6, 7 and 14 were exclusive to LBM, while QTL on chrs 4 and 11 were exclusively body length. LBM QTL on chrs 2 and 9 overlap with those of size. Altogether, the ten LBM QTL explained 41.2% of phenotypic variance in F(2) mice. Five significantly interacting loci that may be involved in the regulation of LBM were identified and accounted for 24.4% of phenotypic variance explained by the QTL. Five epistatic interactions, contributing 22.9% of phenotypic variance, were identified for body length. Interacting loci on chr 2 may influence LBM by regulating body length. Therefore, epistatic interactions as well as single QTL effects play an important role in the regulation of LBM.

Quantitative trait loci that harbor genes regulating muscle size in (MRL/MPJ x SJL/J) F(2) mice.

The genetic mechanisms that determine muscle size have not been elucidated, even though it is a key musculoskeletal parameter that reflects muscle strength. In this study, we performed a high-density genome-wide scan using 633 (MRL/MPJ x SJL/J) F(2) intercross 7-week-old mice to identify quantitative trait loci (QTL) involved in the determination of muscle size. Significant QTL were identified for muscle size and body length. Muscle size (adjusted by body length) QTL were identified on chromosomes 7, 9, 11, 14 (two QTL) and 17, which together explained 19.2% of phenotypic variance in F(2)mice, while body length QTL were located on chromosome 2 (two QTL), 9, 11 and 17 which accounted for 28.3% of phenotypic variance in F(2) mice. Three significant epistatic interactions between different QTL positions from muscle size and body length were identified ( P <0.01) on chromosomes 2, 9, 14 and 17, which explained 16.1% of the variance in F(2) mice.

Chromosomal regions harboring genes for the work to femur failure in mice.

The work to failure is defined as the maximum energy bone can absorb before breaking, and therefore is a direct test of the risk of fracture. To determine the genetic loci influencing work to failure, we have performed a high density genome-wide scan in 633 (MRL x SJL) F(2) female mice. Five loci ( P<0.005) with significant effects on work to failure were found on chromosomes 2, 7, 8, 9, and X, which collectively explained around 20% variance of work to femur failure in F(2) mice. Of those, only the QTL on chromosome 9 was concordant with bone mineral density (BMD) QTLs. Eight significant interactions ( P<0.01) between marker loci were identified, which accounted for an equivalent amount of F(2) variance (23%) to combined single QTL effects. Our results demonstrate that most of the genetic loci regulating work to failure are different from those for BMD in the 7-week-old female mice. If this is also true in humans, this finding will challenge the predictive value of BMD for the risk of fracture.