RNAseq analysis of skeletal muscle transcriptomes from non-transgenic (NTG) and skeletal muscle specific overexpression a deletion mutant form of ornithine transcarbamylase (MCK-?OTC) mice.

We analyzed the gene expression changes that result from mitochondria overloaded by unfolded proteins in skeletal muscles. Mitochondrial-retained mutant ornithine transcarbamylase (?OTC) is a known protein degraded by LONP1 and an established model for studying mitochondrial proteostasis imbalance. We generated transgenic mice overexpressing ?OTC specifically in skeletal muscle using the muscle creatine kinase promoter (MCK-?OTC). Transcriptome analysis was performed by whole-genome gene expression profiling experiments in muscles from the MCK-?OTC mice and NTG littermate controls. The comparative mRNA profiling strategy revealed extensive genomic reprogramming in MCK-?OTC muscles, with 1051 genes up- and 519 genes down-regulated (1.5-fold change and p<0.05), respectively. GO analysis of the regulated genes in MCK-?OTC muscles revealed significant enrichment in unfolded protein response as well as RNA processing process. These data suggest that mitochondria overloaded by ?OTC unfolded proteins induce extensive genomic reprogramming in skeletal muscle Overall design: Gastrocnemius muscle mRNA profiles of 2-week-old NTG and MCK-?OTC mice were generated by deep sequencing, in duplicate, using Illumina HiSeq 4000.