Engelbeen Sarah, Aartsma-Rus Annemieke, Koopmans Bastijn, Loos Maarten, van Putten Maaike
Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
Sylics (Synaptologics B.V.), Amsterdam, Netherlands.
Front Behav Neurosci. 2021 Jan 20;14:629043. doi: 10.3389/fnbeh.2020.629043. eCollection 2020.
Duchenne muscular dystrophy (DMD) is a severe, progressive neuromuscular disorder caused by mutations in the gene resulting in loss of functional dystrophin protein. The muscle dystrophin isoform is essential to protect muscles from contraction-induced damage. However, most dystrophin isoforms are expressed in the brain. In addition to progressive muscle weakness, many DMD patients therefore also exhibit intellectual and behavioral abnormalities. The most commonly used mouse model for DMD, the mouse, lacks only the full-length dystrophin isoforms and has been extensively characterized for muscle pathology. In this study, we assessed behavioral effects of a lack of full-length dystrophins on spontaneous behavior, discrimination and reversal learning, anxiety, and short-term spatial memory and compared performance between male and female mice. In contrast to our previous study using only female mice, we could not reproduce the earlier observed reversal learning deficit. However, we did notice small differences in the number of visits made during the Y-maze and dark-light box. Results indicate that it is advisable to establish standard operating procedures specific to behavioral testing in mice to allow the detection of the subtle phenotypic differences and to eliminate inter and intra laboratory variance.
杜兴氏肌肉营养不良症（DMD）是一种严重的进行性神经肌肉疾病，由基因突变导致功能性肌营养不良蛋白缺失引起。肌肉肌营养不良蛋白亚型对于保护肌肉免受收缩诱导的损伤至关重要。然而，大多数肌营养不良蛋白亚型在大脑中表达。因此，除了进行性肌肉无力外，许多DMD患者还表现出智力和行为异常。最常用于DMD研究的小鼠模型，即mdx小鼠，仅缺乏全长肌营养不良蛋白亚型，并且已对其肌肉病理学进行了广泛的表征。在本研究中，我们评估了缺乏全长肌营养不良蛋白对自发行为、辨别和逆向学习、焦虑以及短期空间记忆的行为影响，并比较了雄性和雌性mdx小鼠的表现。与我们之前仅使用雌性mdx小鼠的研究不同，我们无法重现早期观察到的逆向学习缺陷。然而，我们确实注意到在Y迷宫和明暗箱实验中访问次数存在细微差异。结果表明，建议建立特定于mdx小鼠行为测试的标准操作程序，以便检测细微的表型差异并消除实验室间和实验室内的差异。
