Südkamp Nicolina, Heinen-Weiler Jacqueline, Rohm Marlena, Zaik Michaela, Daya Nassam, Güttsches Anne-Katrin, Theiss Carsten, Roos Andreas, Ruck Tobias, Jacobsen Frank, Schlaffke Lara, Vorgerd Matthias
Department of Neurology, BG-University Hospital Bergmannsheil gGmbH, Ruhr University Bochum, Bochum, Germany.
Heimer Institute for Muscle Research, BG-University Hospital Bergmannsheil gGmbH, Bochum, Germany.
Sci Rep. 2025 Sep 12;15(1):32507. doi: 10.1038/s41598-025-17742-3.
Establishing well-described mouse models of hereditary diseases is increasingly important for testing new therapeutic approaches, such as gene replacement therapy. In particular, a detailed description of muscle pathology, especially at early timepoints of the disease, is crucial for determining the optimal timepoint for drug delivery and evaluation of therapeutic success. In this study, we aimed to characterize and quantify the muscle pathology and myofibre morphology of different muscles in a new mouse model for calpainopathy as an example of the heterogenous group of limb girdle muscular dystrophies compared to wildtype controls during the disease. We analysed motor function and muscle tissue of wildtype and Capn3-transgenic mice per gender from 1.5 to 15 months of age. While transgenic mice did not develop restrictions in motor function, tested with grip strength measurement, beam walk and four limb wire hanging test, during this period, gastrocnemius, soleus and psoas muscles showed progressive histopathological and ultrastructural changes. Importantly, we also detected gender-specific differences in general muscle structure and in muscle pathology in the mouse model of calpainopathy. We developed a score to classify pathology of muscles in this mouse model using percentage of myocytes with centralized nuclei to increase objectivity and comparability when using this mouse model.
建立描述清晰的遗传性疾病小鼠模型对于测试新的治疗方法（如基因替代疗法）越来越重要。特别是，详细描述肌肉病理学，尤其是在疾病的早期时间点，对于确定药物递送的最佳时间点和评估治疗效果至关重要。在本研究中，我们旨在以一种新的钙蛋白酶病小鼠模型为例，与野生型对照相比，在疾病期间表征和量化不同肌肉的肌肉病理学和肌纤维形态，钙蛋白酶病是肢带型肌营养不良异质性组的一个例子。我们分析了1.5至15月龄野生型和Capn3转基因小鼠按性别分类的运动功能和肌肉组织。在此期间，虽然通过握力测量、梁式行走和四肢悬垂试验测试，转基因小鼠的运动功能没有出现受限情况，但腓肠肌、比目鱼肌和腰大肌显示出进行性组织病理学和超微结构变化。重要的是，我们还在钙蛋白酶病小鼠模型中检测到一般肌肉结构和肌肉病理学方面的性别差异。我们开发了一个评分系统，使用具有中央核的肌细胞百分比对该小鼠模型中的肌肉病理学进行分类，以在使用该小鼠模型时提高客观性和可比性。
