Dystonia musculorum (dt) mice, which have a mutation in the Dystonin (Dst) gene, are used as animal models to investigate the human disease known as hereditary sensory and autonomic neuropathy type VI. Massive neuronal cell death is observed, mainly in the peripheral nervous system (PNS) of dt mice. We and others have recently reported a histopathological feature of these mice that neurofilament (NF) accumulates in various areas of the central nervous system (CNS), including motor pathways. Although dt mice show motor disorder and growth retardation, the causes for these are still unknown. Here we performed histopathological analyses on motor units of the trigeminal motor nucleus (Mo5 nucleus), because they are a good system to understand neuronal responses in the mutant CNS, and abnormalities in this system may lead to problems in mastication, with subsequent growth retardation. We report that motoneurons with NF accumulation in the Mo5 nuclei of Dst^Gt homozygous mice express the stress-induced genes CHOP, ATF3, and lipocalin 2 (Lcn2). We also show a reduced number of Mo5 motoneurons and a reduced size of Mo5 nuclei in Dst^Gt homozygous mice, possibly due to apoptosis, given the presence of cleaved caspase 3-positive Mo5 motoneurons. In the mandibular (V3) branches of the trigeminal nerve, which contains axons of Mo5 motoneurons and trigeminal sensory neurons, there was infiltration of Iba1-positive macrophages. Finally, we report atrophy of the masseter muscles in Dst^Gt homozygous mice, which showed abnormal nuclear localization of myofibrils and increased expression of atrogin-1 mRNA, a muscle atrophy-related gene and weaker masseter muscle strength with uncontrolled muscle activity by electromyography (EMG). Taken together, our findings strongly suggest that mastication in dt mice is affected due to abnormalities of Mo5 motoneurons and masseter muscles, leading to growth retardation at the post-weaning stages.

肌张力障碍（DT）小鼠，其具有在一个突变Dystonin（Dst的）基因，用作动物模型，研究被称为遗传性感觉和自主神经病变类型VI的人类疾病。观察到大量神经元细胞死亡，主要发生在dt小鼠的外周神经系统（PNS）中。我们和其他人最近报告了这些小鼠的组织病理学特征，其中神经丝（NF）累积在中枢神经系统（CNS）的各个区域，包括运动通路。虽然dt小鼠表现出运动障碍和生长迟缓，其原因尚不清楚。在这里，我们对三叉神经运动核（Mo5核）的运动单位进行了组织病理学分析，因为它们是了解突变型CNS中神经元反应的良好系统，并且该系统的异常可能会导致咀嚼问题，并随后导致发育迟缓。我们报告说，在Dst ^Gt纯合小鼠的Mo5核中具有NF积累的运动神经元表达应激诱导的基因CHOP，ATF3和lipocalin 2（Lcn2）。我们还显示了Dst ^Gt中Mo5运动神经元的数量减少和Mo5核大小的减少纯合小鼠，可能是由于凋亡引起的，胱天蛋白酶3阳性的Mo5运动神经元被裂解。在包含Mo5运动神经元轴突和三叉感觉神经元的三叉神经的下颌（V3）分支中，有Iba1阳性巨噬细胞浸润。最后，我们报道了Dst ^Gt纯合小鼠的咬肌萎缩，表现为肌原纤维异常核定位和atrogin-1 mRNA的表达增加，肌肉萎缩相关基因和较弱的咬肌强度，而肌电图显示肌电活动不受控制（EMG） ）。两者合计，我们的发现强烈表明dt中的咀嚼 Mo5运动神经元和咬肌的异常会影响小鼠，导致断奶后阶段的发育迟缓。