Effect of muscular dystrophy caused by PTRF deletion on the transcriptome of skeletal muscles

Muscular dystrophy is a group of diseases that cause progressive weakness and degeneration of the skeletal muscles that control movement. Lacking the caveolae component polymerase I transcription release factor (PTRF) causes a secondary deficiency of caveolins resulting in muscular dystrophy. To investigate the effect of PTRF deletion on skeletal muscle, we created gene-edited mice with PTRF knockout (KO). We then performed RNA-seq of soleus and quadriceps muscles from soleus and quadriceps muscles of 3 months old WT (n=3) and PTRF KO mice (n=3) and analyzed the data for gene expression profiling. 12933 genes were detected across all 12 libraries. The hierarchy clustering of co-expressed genes revealed a clear split between PTRF KO and WT mice for both skeletal muscles. Differential expression analysis identified 1293 and 705 differentially expressed genes (DEGs) in the soleus and quadriceps, respectively. 971 and 534 DEGs were up-regulated, and 322 and 171 DEGs were down-regulated in the soleus and quadriceps of PTRF KO mice, respectively. Gene expression profiling analysis of mRNA-seq data for normal muscles and PTRF knockout muscles (soleus and quadriceps).肌营养不良症（Muscular dystrophy）是一类可导致支配躯体运动的骨骼肌出现进行性无力与退行性病变的疾病群。缺乏膜穴（caveolae）组分聚合酶I转录释放因子（PTRF）会引发膜穴蛋白继发性缺失，进而诱发肌营养不良症。为探究PTRF敲除对骨骼肌的影响，我们构建了PTRF基因敲除（knockout, KO）基因编辑小鼠。随后，我们对3月龄野生型（wild type, WT，n=3）与PTRF敲除小鼠（n=3）的比目鱼肌与股四头肌开展RNA测序，并对测序数据进行基因表达谱分析。所有12个测序文库中共检测到12933个基因。共表达基因的层级聚类分析显示，两种骨骼肌的PTRF敲除组与野生型组均呈现清晰的聚类分离。差异表达分析结果显示，比目鱼肌与股四头肌中分别鉴定出1293个与705个差异表达基因（differentially expressed genes, DEGs）。在PTRF敲除小鼠的比目鱼肌与股四头肌中，分别有971个与534个差异表达基因上调，322个与171个差异表达基因下调。本研究针对正常骨骼肌与PTRF敲除骨骼肌（比目鱼肌与股四头肌）的mRNA测序数据开展了基因表达谱分析。