Muscle transcriptome in mouse models of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that is most often caused by mutations in collagen type I encoding genes. Even though bone fragility is the most conspicuous finding in OI, the muscle system is also affected. In the present study we explored the muscle phenotype related to collagen type I mutations on the transcriptome level. RNA sequencing was performed in gastrocnemius muscles of homozygous oim mice and of heterozygous Jrt mice, two models of severe OI. We found that oim and Jrt mice shared 27 differentially expressed genes, of which 11 were concordantly upregulated and 15 concordantly downregulated. Gene Set Enrichment Analysis revealed that in both oim and Jrt mice, genes involved in 'metabolism of lipids' were significantly enriched among upregulated genes. In addition, several genes coding for extracellular matrix components were upregulated in both oim and Jrt mice. Among downregulated genes, genes involved in 'muscle contraction' were enriched in both OI mouse models. These 'muscle contraction' genes coded for slow-twitch type I muscle fiber components. Another shared downregulated gene was Mss51, a metabolic stress-inducible factor that is found in mitochondria. These data show that two mouse models of severe OI share abnormalities in the expression of genes that code for extracellular matrix proteins, lipid and energy metabolism and structural proteins of type I muscle fibers. The muscle disturbances resulting from the collagen type I mutations in these mouse models could be viewed as a mild form of muscle dystrophy.