Verhaeg Minou A T, van der Pijl Elizabeth M, van de Vijver Davy, Winter Christa L Tanganyika-de, Stan Tiberiu L, van Uffelen Angel, Censoni Luciano, van Putten Maaike
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
The Group for Integrative Neurophysiology, Department of Medical and Translational Biology, Umeå University, 901 87 Umeå, Sweden.
Dis Model Mech. 2025 Feb 1;18(2). doi: 10.1242/dmm.052047. Epub 2025 Mar 3.
Duchenne muscular dystrophy is a severe neuromuscular disorder, caused by mutations in the DMD gene. Normally, the DMD gene gives rise to many dystrophin isoforms, of which multiple are expressed in the brain. The location of the mutation determines the number of dystrophin isoforms affected, and the absence thereof leads to behavioral and cognitive impairments. Even though behavioral studies have thoroughly investigated the effects of the loss of Dp427, and to a lesser extent of Dp140, in mice, direct comparisons between models lacking multiple dystrophin isoforms are sparse. Furthermore, a behavioral characterization of the DMD-null mouse, which lacks all dystrophin isoforms, has never been undertaken. Using a wide variety of behavioral tests, we directly compared impairments between mdx5cv, mdx52 and DMD-null mice. We confirmed the role of Dp427 in emotional reactivity. We did not find any added effects of loss of Dp140 on fear, but showed the involvement of Dp140 in spontaneous behavior, specifically in habituation and activity changes due to light/dark switches. Lastly, our results indicate that Dp71/Dp40 play an important role in many behavioral domains, including anxiety and spontaneous behavior.
杜兴氏肌营养不良症是一种严重的神经肌肉疾病，由DMD基因突变引起。正常情况下，DMD基因会产生多种肌营养不良蛋白亚型，其中多种在大脑中表达。突变的位置决定了受影响的肌营养不良蛋白亚型的数量，而其缺失会导致行为和认知障碍。尽管行为学研究已经深入调查了小鼠中Dp427缺失的影响，以及在较小程度上Dp140缺失的影响，但缺乏多种肌营养不良蛋白亚型的模型之间的直接比较却很少。此外，从未对缺乏所有肌营养不良蛋白亚型的DMD基因敲除小鼠进行过行为特征描述。我们使用了多种行为测试，直接比较了mdx5cv、mdx52和DMD基因敲除小鼠之间的损伤情况。我们证实了Dp427在情绪反应中的作用。我们没有发现Dp140缺失对恐惧有任何额外影响，但表明Dp140参与自发行为，特别是在因明暗转换引起的习惯化和活动变化中。最后，我们的结果表明，Dp71/Dp40在包括焦虑和自发行为在内的许多行为领域中发挥着重要作用。
