Numerous candidate genes have been suggested in the recent literature with proposed roles in regulation of voluntary physical activity, with little evidence of these genes' functional roles. This study compared the haplotype structure and expression profile in skeletal muscle and brain of inherently high- (C57L/J) and low- (C3H/HeJ) active mice. Expression of nine candidate genes [Actn2, Actn3, Casq1, Drd2, Lepr, Mc4r, Mstn, Papss2, and Glut4 (a.k.a. Slc2a4)] was evaluated via RT-qPCR. SNPs were observed in regions of Actn2, Casq1, Drd2, Lepr, and Papss2; however, no SNPs were located in coding sequences or associated with any known regulatory sequences. In mice exposed to a running wheel, Casq1 (P = 0.0003) and Mstn (P = 0.002) transcript levels in the soleus were higher in the low-active mice. However, when these genes were evaluated in naïve animals, differential expression was not observed, demonstrating a training effect. Among naïve mice, no genes in either tissue exhibited differential expression between strains. Considering that no obvious SNP mechanisms were determined or differential expression was observed, our results indicate that genomic structural variation or gene expression data alone is not adequate to establish any of these genes' candidacy or causality in relation to regulation of physical activity.
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. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit transcription by binding to a target gene, inhibiting protein production. The purpose of this study was to investigate differential miRNA 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 miRNA microarray analysis, and selected miRNAs were validated by qRT-PCR. Expression of 13 miRNAs varied between strains in the nucleus accumbens, 20 in soleus, and eight in EDL, by microarray analysis. Two miRNAs 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 miRNA families with sequence located in intron 10 of Sfmbt2; miRNAs at this locus are thought to drive imprinting of this gene. “Pathways in cancer” and “TGFβ 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 miRNA expression between high- and low-active mice, and suggest that miRNAs may play a role in regulation of physical activity.
Studies of dietary effects on heterosis for body weight gain (BWG) and feed conversion ratio (FCR) are few. In the present work, heterosis, heterosis due to sex chromosome, and maternal and line effects for BWG and FCR were compared in reciprocal crosses of White Plymouth Rock (WPR) and Single Comb White Leghorn (SCWL). These birds were reared on either 18 or 20% crude protein (CP) diets from hatch to 8 weeks. The WPR birds exhibited larger body weights and consumed more feed than the SCWL birds. Also WPR birds on 20% CP diet were larger than those on 18% CP diet. Although FCR of SCWL birds on 18% CP diet was lower than those on 20% CP diet at 1 and 3-6 weeks, FCR was lower in WPR than SCWL birds. Heterosis was higher at 18% CP diets and the average maternal and line effects for BWG were higher (P<0.05) for WPR than SCWL and at 18 than 20% CP diets. However, maternal effects for FCR of WPR progeny were higher at 20 than 18% CP diets. Average line effects were also higher for WPR than SCWL males and significant at 20% CP diets for both lines. Heterosis due to sex chromosome was significant (PO.05) and positive for BWG but negative for FCR. This study indicates that SCWL males and WPR females exhibited higher combining ability at 18 than 20% CP diets. The significant heterosis for BWG and FCR due to sex chromosomes and maternal effects suggest that these two traits are also affected by genes on the sex chromosome.
This study investigated the levels of gene expression for eight potential candidate genes speculated to play a role in voluntary physical activity: Leptin Receptor (Lepr), Actinin alpha 2 (Actn), Myostatin (Mstn), Calsequestrin1 (Casq1), Dopamine Receptor 1 (Drd1), Nescient helix loop helix 2 (Nhlh2), and Glucose Transporter member 4 (Slc2a4) in soleus and nucleus accumbens of high active (C57L/J, n=3) and low active (C3H/HeJ, n=4) inbred mice as well as high (n=16) and low active (n=18) F2 offspring. All animal procedures were conducted in conformance with the FASEB Statement of Principles for the use of animals in research and education. The F2 cohort was used as a control to remove gene expression due to the homozygosity of the inbred animals. mRNA was isolated and quantitative real‐time PCR was performed. Gene expression was calculated as a ratio of the cross point (ct) of the target gene to RN18S (control gene). Mstn (p=0.02) and Casq1 (p=0.04) had higher expression in the soleus of low active animals. Mstn was also found to be differentially expressed in soleus between the high and low active F2 animals (p=.045), as well as between the progenitors (p=.03), when the groups were analyzed separately. While other genes may also regulate activity, none appear to function by differences in transcriptional product as do Mstn and Casq1 in this study. This work is supported by Texas A&M University.
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