Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin.
Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin.
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DOI：
10.1371/journal.pone.0152413
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Reid E
中科院分区：
文献类型：
--
作者：
Connell JW;Allison R;Reid E
遗传性痉挛性截瘫是一种皮质脊髓束进行性轴突变性的遗传性疾病。编码微管切断ATP酶痉挛蛋白的基因中的常染色体显性突变，包括无义、移码和错义变化，是北美和北方欧洲HSP的最常见原因。在这项研究中，我们报告定量步态分析使用电动跑步机系统，进行小鼠敲入的疾病相关的突变影响的关键残基的步行者A基序的痉挛蛋白ATP酶结构域。在4个月和1岁时，与杂合子和野生型同窝小鼠相比，纯合子突变小鼠具有许多异常步态参数，包括步幅长度和步幅持续时间。杂合子动物的步态参数与野生型同窝仔没有差异。我们得出结论，定量步态分析使用DigiGait系统灵敏地检测运动异常的遗传性痉挛性截瘫模型，并将是一个有用的方法，用于分析HSP的药物治疗的效果。
The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP.