been numerous advances in the fi eld, many aspects of the pathology and disease progression over time are still unclear. Here, we have utilised high-resolution isoelectric focusing liquid chromatography-mass spectrometry… Click to show full abstract
been numerous advances in the fi eld, many aspects of the pathology and disease progression over time are still unclear. Here, we have utilised high-resolution isoelectric focusing liquid chromatography-mass spectrometry (HiRIEF-LCMS/MS; using isobaric labelling with tandem mass tag (TMT) chemistry) to investigate diff erential protein expression in the tibialis anterior (TA) of mdx, mdx52 and wild-type controls (C57BL/6) at 8, 16 and 80 weeks of age. This technique has provided improved resolution of the proteome, whereby a total of 4974 proteins were detected in all samples. Only small diff erences in protein expression were observed between mdx and mdx52. Therefore, these two strains were grouped into “dystrophic” to allow investigation of altered pathways that are common to a dystrophic model, irrespective of mutation. This analysis showed clear diff erences between the control and dystrophic mice with 2148 proteins diff erentially expressed (t-Test, P=0.01). Additionally, protein expression changed signifi cantly with ageing for both groups. These studies off er a view of the dystrophic proteome with unprecedented resolution and provide fundamental new insights into processes occurring in dystrophic muscle, with potential therapeutic implications.
               
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