title: Genetic and genomic analyses of musculoskeletal differences between BEH and BEL strains.
abstract: Berlin high (BEH) and Berlin low (BEL) strains selected for divergent growth differ threefold in body weight. We aimed at examining muscle mass, which is a major contributor to body weight, by exploring morphological characteristics of the soleus muscle (fiber number and cross sectional area; CSA), by analyzing the transcriptome of the gastrocnemius and by initiating quantitative trait locus (QTL) mapping. BEH muscles were four to eight times larger than those of BEL. In substrain BEH+/+, mutant myostatin was replaced with a wild-type allele; however, BEH+/+muscles still were two to four times larger compared with BEL. BEH soleus muscle fibers were two times more numerous (P < 0.0001) and CSA was two times larger (P < 0.0001) compared with BEL. In addition, soleus femoral attachment anomaly (SFAA) was observed in all BEL mice. One significant (Chr 1) and four suggestive (Chr 3, 4, 6, and 9) muscle weight QTLs were mapped in a 21-day-old F2 intercross (n = 296) between BEH and BEL strains. The frequency of SFAA incidence in the F2 and in the backcross to BEL strain (BCL) suggested the presence of more than one causative gene. Two suggestive SFAA QTLs were mapped in BCL; however, their peak markers were not associated with the phenotype in F2. RNA-Seq analysis revealed 2,148 differentially expressed (P < 0.1) genes and 45,673 single nucleotide polymorphisms and >2,000 indels between BEH+/+ and BEL males. In conclusion, contrasting muscle traits and genomic and gene expression differences between BEH and BEL strains provide a promising model for the search for genes involved in muscle growth and musculoskeletal morphogenesis.
authors: School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom;
authors: Arimantas
authors: A
authors: Lionikas
authors: Audrius
authors: A
authors: Kilikevicius
authors: Lutz
authors: L
authors: Bünger
authors: Caroline
authors: C
authors: Meharg
authors: Andrew M
authors: AM
authors: Carroll
authors: Aivaras
authors: A
authors: Ratkevicius
authors: Tomas
authors: T
authors: Venckunas
authors: David A
authors: DA
authors: Blizard
mesh_terms: D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D005838:Genotype; D006614:Hindlimb / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D009141:Musculoskeletal System / Q000378:metabolism*; D009929:Organ Size / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics
keywords: QTL mapping; skeletal muscle; transcriptome
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