Duchenne muscular dystrophy (DMD) is caused by the loss of dystrophin. Severe and ultimately lethal, DMD progresses relatively slowly in that patients become wheelchair bound only around age twelve with a survival expectancy reaching the third decade of life. The mildly-affected mouse model of DMD, and transgenic DysΔMTB- and Fiona- mice expressing dystrophin or utrophin, respectively, were exposed to either mild (scruffing) or severe (subordination stress) stress paradigms and profiled for their behavioral and physiological responses. A subgroup of mice exposed to subordination stress were pretreated with the beta-blocker metoprolol. Subordination stress caused lethality in ∼30% of mice within 24 h and ∼70% lethality within 48 h, which was not rescued by metoprolol. Lethality was associated with heart damage, waddling gait and hypo-locomotion, as well as marked up-regulation of the hypothalamus-pituitary-adrenocortical axis. A novel cardiovascular phenotype emerged in mice, in that scruffing caused a transient drop in arterial pressure, while subordination stress caused severe and sustained hypotension with concurrent tachycardia. Transgenic expression of dystrophin or utrophin in skeletal muscle protected mice from scruffing and social stress-induced responses including mortality. We have identified a robust new stress phenotype in the otherwise mildly affected mouse that suggests relatively benign handling may impact the outcome of behavioural experiments, but which should also expedite the knowledge-based therapy development for DMD. Greg Marzolf Jr. Foundation, Summer's Wish Fund, NIAMS, Muscular Dystrophy Association, University of Minnesota and John and Cheri Gunvalson Trust.

中文翻译：

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社会压力在杜氏肌营养不良症的 mdx 模型中是致命的

杜氏肌营养不良症 (DMD) 是由肌营养不良蛋白缺失引起的。 DMD 严重且最终致命，进展相对缓慢，患者仅在 12 岁左右开始坐轮椅，预期生存期可达 30 岁。轻度 DMD 小鼠模型以及分别表达抗肌营养不良蛋白或肌营养不良蛋白的转基因 DysΔMTB 和 Fiona 小鼠暴露于轻度（扭伤）或重度（服从应激）应激模式，并对其行为和生理反应进行分析。一组暴露于从属压力的小鼠接受β受体阻滞剂美托洛尔预处理。服从应激导致约 30% 的小鼠在 24 小时内死亡，约 70% 的小鼠在 48 小时内死亡，美托洛尔无法挽救这种情况。致死率与心脏损伤、蹒跚步态和运动不足以及下丘脑-垂体-肾上腺皮质轴的显着上调有关。小鼠中出现了一种新的心血管表型，即扭动导致动脉压短暂下降，而服从应激则导致严重且持续的低血压并伴有心动过速。骨骼肌中肌营养不良蛋白或肌营养不良蛋白的转基因表达可保护小鼠免受扭伤和社会压力引起的反应（包括死亡）。我们在受到轻微影响的小鼠中发现了一种强大的新应激表型，这表明相对良性的处理可能会影响行为实验的结果，但这也应该会加快 DMD 的基于知识的治疗的开发。 Greg Marzolf Jr. 基金会、Summer's Wish 基金、NIAMS、肌肉萎缩症协会、明尼苏达大学以及 John 和 Cheri Gunvalson 信托基金。