| First Author | Hardee JP | Year | 2021 |
| Journal | Am J Physiol Cell Physiol | Volume | 321 |
| Issue | 2 | Pages | C288-C296 |
| PubMed ID | 34191629 | Mgi Jnum | J:310502 |
| Mgi Id | MGI:6720945 | Doi | 10.1152/ajpcell.00188.2021 |
| Citation | Hardee JP, et al. (2021) Dystrophin deficiency disrupts muscle clock expression and mitochondrial quality control in mdx mice. Am J Physiol Cell Physiol |
| abstractText | Impaired oxidative capacity and mitochondrial function contribute to the dystrophic pathology in muscles of Duchenne muscular dystrophy (DMD) patients and in relevant mouse models of the disease. Emerging evidence suggests an association between disrupted core clock expression and mitochondrial quality control, but this has not been established in muscles lacking dystrophin. We examined the diurnal regulation of muscle core clock and mitochondrial quality control expression in dystrophin-deficient C57BL/10ScSn-Dmd(mdx) (mdx) mice, an established model of DMD. Male C57BL/10 (BL/10; n=18) and mdx mice (n=18) were examined every 4 hours beginning at the dark cycle. Throughout the entire light-dark cycle, extensor digitorum longus (EDL) muscles from mdx mice had decreased core clock mRNA expression (Arntl, Cry1, Cry2, Nr1d2; p<0.05) and disrupted mitochondrial quality control mRNA expression related to biogenesis (decreased; Ppargc1a, Esrra; p<0.05), fission (increased; Dnm1l; p<0.01), fusion (decreased; Opa1, Mfn1; p<0.05) and autophagy/mitophagy (decreased: Bnip3; p<0.05; increased: Becn1; p<0.05). Cosinor analysis revealed a decrease in the rhythmicity parameters mesor and amplitude for Arntl, Cry1, Cry2, Per2, and Nr1d1 (p<0.001) in mdx mice. Diurnal oscillations in Esrra, Sirt1, Map1lc3b and Sqstm1 were absent in mdx mice, along with decreased mesor and amplitude of Ppargc1a mRNA expression (p<0.01). The expression of proteins involved in mitochondrial biogenesis (decreased: PPARGC1A, p<0.05) and autophagy/mitophagy (increased: MAP1LC3BII, SQSTM1, BNIP3; p<0.05) were also dysregulated in tibialis anterior muscles of mdx mice. These findings suggest that dystrophin deficiency in mdx mice impairs the regulation of the core clock and mitochondrial quality control, with relevance to DMD and related disorders. |
