Hawkins India K, Phi Trung, Mitchell Joshua, Corwin Frank, Mauro Adolfo G, Salloum Fadi N, Raucci Frank J
Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Richmond at Virginia Commonwealth University, Richmond, Virginia, USA.
Bioimaging and Applied Research Core, Virginia Commonwealth School of Medicine, Richmond, Virginia, USA.
FASEB J. 2025 Jul 31;39(14):e70850. doi: 10.1096/fj.202500792R.
Duchenne Muscular Dystrophy (DMD) is a progressive muscular degenerative disease that is recessively inherited through the X chromosome. Various mutations in the dystrophin gene lead to noticeable muscle weakness. The effects on skeletal and cardiac tissue result in progressive immobility and cardiac dysfunction, respectively. There are several murine models used to study DMD; however, there are still limitations in replicating the pathology of the disease seen in humans with DMD. Myh6cre(Cre) genotypic modification through the Cre/LoxP system has been proposed to further develop the pathology in murine models to specifically target cardiac tissue while allowing further alteration downstream in the mouse's lifespan. Initial observation of obesity in conjunction with premature death compared to traditional dystrophin-affected mice prompted us to take a further look into fibrosis and cardiac dysfunction. Our findings may help define the phenotype of dystrophin knockout, Cre-positive mice and display the potential for a more accurate, pathological model for DMD.
杜兴氏肌肉营养不良症（DMD）是一种进行性肌肉退行性疾病，通过X染色体隐性遗传。肌营养不良蛋白基因的各种突变会导致明显的肌肉无力。对骨骼和心脏组织的影响分别导致进行性运动障碍和心脏功能障碍。有几种小鼠模型用于研究DMD；然而，在复制DMD患者所见疾病的病理学方面仍存在局限性。有人提出通过Cre/LoxP系统进行Myh6cre（Cre）基因修饰，以进一步发展小鼠模型中的病理学，从而特异性靶向心脏组织，同时允许在小鼠寿命的下游进行进一步改变。与传统的受肌营养不良蛋白影响的小鼠相比，最初观察到肥胖与过早死亡相关，这促使我们进一步研究纤维化和心脏功能障碍。我们的发现可能有助于定义肌营养不良蛋白基因敲除、Cre阳性小鼠的表型，并展示建立更准确的DMD病理模型的潜力。
