Genomic analysis of variation in hindlimb musculature of mice from the C57BL/6J and DBA/2J lineage.
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.
Lionikas
Arimantas
A
School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. a.lionikas@abdn.ac.uk
Carlborg
Orjan
O
Lu
Lu
L
Peirce
Jeremy L
JL
Williams
Robert W
RW
Yu
Fushun
F
Vogler
George P
GP
McClearn
Gerald E
GE
Blizard
David A
DA
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D014644:Genetic Variation; D006614:Hindlimb / Q000033:anatomy & histology* / Q000254:growth & development; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020412:Multifactorial Inheritance; D018482:Muscle, Skeletal / Q000002:abnormalities / Q000033:anatomy & histology* / Q000254:growth & development