Genomic analysis of variation in hindlimb musculature of mice from the C57BL/6J and DBA/2J lineage

J Hered. 2010 May-Jun;101(3):360-7. doi: 10.1093/jhered/esq023. Epub 2010 Mar 16.

Abstract

The precise locations of attachment points of muscle to bone-the origin and insertion sites-are crucial anatomical and functional characteristics that influence locomotor performance. Mechanisms that control the development of these interactions between muscle, tendon, and bone are currently not well understood. In a subset of BXD recombinant inbred (RI) strains derived from the C57BL/6J and DBA/2J strains, we observed a soleus femoral attachment anomaly (SFAA) that was rare in both parental strains (Lionikas, Glover et al. 2006). The aim of the present study was to assess suitability of SFAA as a model to study the genetic mechanisms underlying variation in musculoskeletal anatomy. We scored the incidence of SFAA in 55 BXD strains (n = 9 to 136, median = 26, phenotyped animals per strain, for a total number of 2367). Seven strains (BXD1, 12, 38, 43, 48, 54, and 56) exhibited a high incidence of unilateral SFAA (47-89%), whereas 23 strains scored 0%. Exploration of the mechanisms underlying SFAA in 2 high incidence strains, BXD1 and BXD38, indicated that SFAA-relevant genes are to be found in both C57BL/6J and DBA/2J regions of the BXD1 genome. However, not all alleles relevant for the expression of the phenotype were shared between the 2 high-incidence BXD strains. In conclusion, the anatomical origin of the soleus muscle in mouse is controlled by a polygenic system. A panel of BXD RI strains is a useful tool in exploring the genetic mechanisms underlying SFAA and improving our understanding of musculoskeletal development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromosome Mapping
  • Crosses, Genetic
  • Female
  • Genetic Variation*
  • Hindlimb / anatomy & histology*
  • Hindlimb / growth & development
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Multifactorial Inheritance
  • Muscle, Skeletal / abnormalities
  • Muscle, Skeletal / anatomy & histology*
  • Muscle, Skeletal / growth & development