Regenerated mdx mouse skeletal muscle shows differential mRNA expression

Abstract

Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), beta-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.

Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles

“…DMD and ␣-sarcoglycan deficiencies (17), as well as in muscles of mice after acute ischemia (72). Expression of the cardiac isoform of troponin T, detected in our study, was upregulated in skeletal muscles after both denervation and cold injury (80), and in muscles of DMD patients (6) and mdx mice (91). Troponin T was upregulated during myoblast differentiation (67,80).…”

“…Calsequestrin-2, a calcium-sequestering protein, was upregulated in muscles of DMD patients (6,43) and mdx mice (91). Activation of this gene is related to changes from fast-to slow-twitch phenotype during skeletal muscle regeneration and dystrophy (6).…”

Comparative transcriptome analysis of muscular dystrophy models Largemyd, Dmdmdx/Largemyd and Dmdmdx: what makes them different?

“…Several transcriptome studies in Dmd mdx mouse were published in the last years, [12][13][14][15][16][17][18][19][20] but no studies in Large myd − / − nor in Dmd mdx /Large myd − / − were performed. 9 In Dmd mdx , similar data to the observed in our study were described by Boer et al 14 and Porter et al 17,21 Using an Affymetrix chip of about 12 000 genes/EST, Boer et al 14 identified 58 DEGs in Dmd mdx limb muscles, from which 49 were unregulated while only 9 were downregulated.…”

Myosin accumulation and striated muscle myopathy result from the loss of muscle RING finger 1 and 3

“…This suggests that other MHC-degrading mechanisms, most likely non-proteasome dependent, may be activated in DKO muscle but are clearly not sufficient for complete MHC degradation. Several proteinases such as trypsin-like serine proteinase (41), calpain (42), cathepsin B/L (43,44), and chymase (44) are activated during muscular dystrophy. In particular, trypsin-like serine proteinase mediates myosin cleavage (41) with myosin breakdown products similar to those we observed in DKO soleus ( Figure 2C).…”