Differential mi RNA expression in inherently high‐ and low‐active inbred mice

Abstract Despite established health benefits of regular exercise, the majority of Americans do not meet the recommended levels of physical activity. While it is known that voluntary activity levels are largely heritable, the genetic mechanisms that regulate activity are not well understood. Micro RNA s (mi RNA s) are small non‐coding RNA s that inhibit transcription by binding to a target gene, inhibiting protein production. The purpose of this study was to investigate differential mi RNA expression between inherently high‐ (C57L/J) and low‐ (C3H/HeJ) active inbred mice in soleus, extensor digitorum longus ( EDL ), and nucleus accumbens tissues. Expression was initially determined by mi RNA microarray analysis, and selected mi RNA s were validated by qRT ‐ PCR . Expression of 13 mi RNA s varied between strains in the nucleus accumbens, 20 in soleus, and eight in EDL , by microarray analysis. Two mi RNA s were validated by qRT ‐ PCR in the nucleus accumbens; miR‐466 was downregulated (~4 fold; P  < 0.0004), and miR‐342‐5p was upregulated (~115 fold; P  < 0.0001) in high‐active mice. MiR‐466 was downregulated (~5 fold; P  < 0.0001) in the soleus of high‐active mice as well. Interestingly, miR‐466 is one of several mi RNA families with sequence located in intron 10 of Sfmbt2 ; mi RNA s at this locus are thought to drive imprinting of this gene. “Pathways in cancer” and “ TGF β signaling” were the most significant pathways of putative target genes in both the soleus and nucleus accumbens. Our results are the first to consider differential mi RNA expression between high‐ and low‐active mice, and suggest that mi RNA s may play a role in regulation of physical activity.