Dysferlin-deficiency has greater impact on function of slow muscles, compared with fast, in aged BLAJ mice

Dysferlinopathies are a form of muscular dystrophy caused by gene mutations resulting in deficiency of the protein dysferlin. Symptoms manifest later in life in a muscle specific manner, although the pathomechanism is not well understood. This study compared the impact of dysferlin-deficiency on in vivo and ex vivo muscle function, and myofibre type composition in slow (soleus) and fast type (extensor digitorum longus; EDL) muscles using male dysferlin-deficient (dysf-/-) BLAJ mice aged 10 months, compared with wild type (WT) C57Bl/6J mice. There was a striking increase in muscle mass of BLAJ soleus (+25%) (pIn vivo measures of forelimb grip strength and wheel running capacity showed no strain differences. Ex vivo measures showed the BLAJ soleus had faster twitch contraction (-21%) and relaxation (-20%) times, and delayed post fatigue recovery (ps0.05); however, for the BLAJ EDL, there was an increased proportion of type IIx MHC isoform (+5.5%) and decreased type IIb isoform (-5.5%) (ps

dysferlinopathy（肌营养不良蛋白缺陷肌病）是一类由基因突变导致dysferlin蛋白缺乏所引发的肌营养不良症。该类疾病多成年起病，呈肌肉特异性表型，但其发病机制尚未完全阐明。本研究以10月龄雄性dysferlin缺陷型（dysf-/-）BLAJ小鼠为模型，并以野生型（WT）C57Bl/6J小鼠作为对照，对比分析了dysferlin缺乏对体内（in vivo）、离体（ex vivo）肌肉功能以及慢肌（比目鱼肌，soleus）和快肌（趾长伸肌，EDL）的肌纤维类型组成的影响。BLAJ小鼠的比目鱼肌质量显著升高25%（p<0.05），体内检测的前肢握力与转轮运动能力未显示品系间差异。离体检测结果显示，BLAJ小鼠的比目鱼肌单收缩时程缩短21%、舒张时程缩短20%，且疲劳后恢复延迟（p<0.05）；而BLAJ小鼠的趾长伸肌则呈现IIx型肌球蛋白重链（MHC）亚型占比升高5.5%、IIb型亚型占比降低5.5%的变化（p<0.05）。