Perry disease (Perry syndrome) is a rare, rapidly progressive, autosomal dominant neurodegenerative disease characterized by parkinsonism, depression/apathy, weight loss, and respiratory symptoms including central hypoventilation. It is caused by missense mutations (e.g. p.G71A) in the DCTN1 gene. We previously generated transgenic mice that expressed human DCTN1^G71A mutant protein under the control of Thy1 promoter. These mice exhibited apathy-like behavior and parkinsonism. However, it is possible that this phenotype was due to a gene-dosage imbalance or transgene insertion position. To circumvent these potential caveats, we have generated a knock-in mouse model carrying a p.G71A mutation in Dctn1. Heterozygous Dctn1^G71A and wild-type littermates were subjected to a battery of behavioral analyses. Furthermore, immunohistochemistry for tyrosine hydroxylase (TH) was performed on brain sections of these mice, and TH signal intensity in substantia nigral neurons was quantified. Dctn1^G71A mice were immobile for longer than wild-type mice of the same age and sex in the tail-suspension test, revealing depressive characteristics. In addition, the beam-walking test and pole test detected motor deficits in Dctn1^G71A female mice. Finally, immunostaining revealed a decrease in TH immunoreactivity in neurons of the substantia nigra in the Dctn1^G71A mice. Collectively, heterozygous Dctn1^G71A mice showed depression-like behavior, motor deficits, and a functional reduction in substantia nigral neurons, as judged by TH immunostaining, thereby exhibiting multiple features of Perry disease. Hence, this mouse model will be useful in elucidating pathological mechanisms of Perry disease and for developing novel therapeutic strategies against it.

佩里病（佩里综合征）是一种罕见的、快速进展的、常染色体显性遗传的神经退行性疾病，其特征是帕金森症、抑郁/冷漠、体重减轻和呼吸系统症状，包括中枢性通气不足。它是由DCTN1基因中的错义突变（egpG71A）引起的。我们之前生成了在 Thy1启动子控制下表达人 DCTN1 ^{G71A突变蛋白的转基因小鼠。}这些老鼠表现出冷漠样行为和帕金森症。然而，这种表型可能是由于基因剂量不平衡或转基因插入位置所致。为了规避这些潜在的警告，我们生成了一个在Dctn1中携带 p.G71A 突变的敲入小鼠模型。杂合 Dctn1 ^G71A并对野生型同窝仔进行了一系列行为分析。此外，对这些小鼠的脑切片进行了酪氨酸羟化酶 (TH) 的免疫组织化学分析，并对黑质神经元中的 TH 信号强度进行了量化。Dctn1 ^G71A小鼠在悬尾试验中比同年龄和性别的野生型小鼠不动的时间更长，显示出抑郁特征。此外，光束行走测试和杆测试检测到 Dctn1 ^G71A雌性小鼠的运动缺陷。^{最后，免疫染色显示 Dctn1 G71A}小鼠黑质神经元的 TH 免疫反应性降低。总的来说，杂合 Dctn1 ^G71A通过 TH 免疫染色判断，小鼠表现出抑郁样行为、运动缺陷和黑质神经元功能降低，从而表现出佩里病的多种特征。因此，该小鼠模型将有助于阐明 Perry 病的病理机制并开发针对它的新治疗策略。