Effect of inbred mouse strain on the transcriptomic response to exercise training

We previously documented differences in responses to exercise training in several inbred mouse strains. The purpose of this study was to determine the effect of inbred mouse strain on the transcriptomic responses to exercise training. Eight-week-old male FVB/NJ (FVB) and C57BL/6J (B6) mice were randomly assigned to sedentary control (SED, n = 6/strain) or exercise training (EX, n = 6/strain) groups. After completing exercise performance testing, EX mice underwent 4 weeks of treadmill training (60 min/d, 5 d/wk) at 65% of maximal speed. All mice completed exercise performance testing after 4 weeks. Plantaris muscle was utilized for transcriptomics. RNAseq was performed using an Illumina NovaSeq with approximately 58 million reads per sample. Differential expression analyses were conducted using the limma-voom Bioconductor pipeline (UC Davis Bioinformatics Core). EX mice from both strains significantly improved exercise time with training. EX FVB mice showed substantially greater improvement (+ 8.8 ± 2.7 min) than EX B6 mice (+ 3.9 ± 0.9 min, P = 0.003), confirming previous findings. Comparing expression levels between strains within SED and EX groups yielded 3,666 and 3,004 differentially expressed genes (DEGs) (adj. P-value < 0.05), respectively. Genes associated with the cytoskeleton in muscle cells (e.g., myosin heavy chain, troponin, integrins) were significantly enriched in both EX and SED groups, implying that the cytoarchitecture of skeletal muscle differs between FVB and B6 strains. The number of differentially expressed genes between EX and SED mice also varied by strain. For FVB, the expression of 542 genes (278, up, 264 down) was significantly different (adj. P-value < 0.05) between EX and SED mice. In contrast, 86 genes (32, up, 54 down) were significantly different (adj. P-value < 0.05) between SED and EX B6 mice. Forty-eight DEGs (23 up, 25 down) were common between strains. Genes involved in immune system function or development, inflammation, and cell migration were downregulated in plantaris muscle from FVB EX mice, including thrombospondin and interleukin-1 receptors. Genes associated with the regulation of transcription and lipid metabolism (e.g., acetyl-Coenzyme A acetyltransferase 1, Acat1 ) were upregulated in plantaris muscle from FVB EX mice. In plantaris muscle from B6 mice, genes regulating transcription (yes-associated protein 1, Yap1 ) and biological rhythms (period circadian clock 1 and 3; Per1, Per3 ) were differentially expressed in EX mice. Although some signaling pathways are responsive to exercise training regardless of mouse strain, these data suggest that the transcriptomic responses to exercise training - both the number of DEGs and the cellular pathways - vary by mouse strain. Texas Tech University Office of Vice President for Research This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.