Splicing changes in gastrocnemius muscle from 3-month-old HSALR mice. Splicing changes in gastrocnemius muscle from 3-month-old HSALR mice

The initial aim of the study was to determine the mechanisms underlying the positive effect of AICAR on the phenotype of HSALR mice, a well-known model for DM1. We have previously shown that treatment with AICAR reduces myotonia and mis-splicing in the HSALR mice. We here aimed to identify splicing and transcriptional changes in gastrocnemius muscle from HSALR mice treated or not with AICAR, as compared to FVB control mice. The data obtained from untreated mice were then used in the study focused on NMJ alterations and CaMKII deregulation in DM1. Overall design: Gastrocnemius muscle from 3-month-old mice. HSALR mice (n= 5 per group); FVB control mice (n=3 per group). Treatment = vehicle or AICAR

本研究的初始目标为阐明AICAR对HSALR小鼠表型的正向调控作用的潜在机制，HSALR小鼠是DM1（肌强直性营养不良1型）的经典模型。我们此前已证实，AICAR处理可减轻HSALR小鼠的肌强直症状并改善其异常剪接缺陷。本研究旨在对比经AICAR处理与未处理的HSALR小鼠、以及FVB对照小鼠的腓肠肌组织中的剪接与转录组变化。本研究中未处理小鼠的相关数据，后续被用于聚焦DM1中神经肌肉接头（Neuromuscular Junction, NMJ）异常与钙/钙调蛋白依赖性蛋白激酶II（Calcium/Calmodulin-dependent Protein Kinase II, CaMKII）失调的相关分析。实验设计概述：取材自3月龄小鼠的腓肠肌；实验分组为HSALR小鼠组（每组n=5）与FVB对照小鼠组（每组n=3）；处理方式分为溶剂对照与AICAR处理两组。