Rapid and robust patterns of spontaneous locomotor deficits in mouse models of Huntington's disease.
Rapid and robust patterns of spontaneous locomotor deficits in mouse models of Huntington's disease.
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DOI：
10.1371/journal.pone.0243052
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Munoz-Sanjuan I
中科院分区：
文献类型：
--
作者：
Heikkinen T;Bragge T;Bhattarai N;Parkkari T;Puoliväli J;Kontkanen O;Sweeney P;Park LC;Munoz-Sanjuan I
亨廷顿病（HD）是一种遗传性神经退行性疾病，其特征在于认知和运动功能的严重破坏，包括姿势和步态的改变。许多HD小鼠模型已经被设计为显示疾病的行为和神经病理学特征，但是这些模型中的步态改变的特征很差。对小鼠精细运动功能和步态进行灵敏的高通量测试可能有助于评估疾病改善干预措施。在这里，我们描述了一个无假设的工作流程，该工作流程可以确定HD R6/2和Q175小鼠模型中79个参数逐渐变化的运动模式。R6/2小鼠（120个CAG重复）早在4周龄时就表现出运动障碍。在3月龄和6月龄的纯合子和杂合子Q175 KI小鼠中分别观察到类似的紊乱。有趣的是，只有R6/2小鼠出现前肢共济失调。行为表型的主成分产生两个表型分数的基础上进行性姿势不稳定的运动学参数和轨迹波形数据，这是共享的两个HD模型。这种方法增加了可用的HD小鼠模型研究工具箱，并有可能促进HD和其他具有高度未满足医疗需求的衰弱性运动障碍的治疗方法的开发。
Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by severe disruption of cognitive and motor functions, including changes in posture and gait. A number of HD mouse models have been engineered that display behavioral and neuropathological features of the disease, but gait alterations in these models are poorly characterized. Sensitive high-throughput tests of fine motor function and gait in mice might be informative in evaluating disease-modifying interventions. Here, we describe a hypothesis-free workflow that determines progressively changing locomotor patterns across 79 parameters in the R6/2 and Q175 mouse models of HD. R6/2 mice (120 CAG repeats) showed motor disturbances as early as at 4 weeks of age. Similar disturbances were observed in homozygous and heterozygous Q175 KI mice at 3 and 6 months of age, respectively. Interestingly, only the R6/2 mice developed forelimb ataxia. The principal components of the behavioral phenotypes produced two phenotypic scores of progressive postural instability based on kinematic parameters and trajectory waveform data, which were shared by both HD models. This approach adds to the available HD mouse model research toolbox and has a potential to facilitate the development of therapeutics for HD and other debilitating movement disorders with high unmet medical need.
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影响因子：
3.2
作者：
Abdi, Herve;Williams, Lynne J.
通讯作者：
Williams, Lynne J.
影响因子：
4.6
作者：
Broom L;Ellison BA;Worley A;Wagenaar L;Sörberg E;Ashton C;Bennett DA;Buchman AS;Saper CB;Shih LC;Hausdorff JM;VanderHorst VG
通讯作者：
VanderHorst VG
DOI：
10.7916/d8qn65gq
发表时间：
2013-01-01
期刊：
Tremor and other hyperkinetic movements (New York, N.Y.)
影响因子：
--
作者：
Defazio, Giovanni;Gigante, Angelo F
通讯作者：
Gigante, Angelo F
影响因子：
6
作者：
Gassner, Heiko;Jensen, Dennis;Kohl, Zacharias
通讯作者：
Kohl, Zacharias
影响因子：
2.4
作者：
Federolf, P. A.;Boyer, K. A.;Andriacchi, T. P.
通讯作者：
Andriacchi, T. P.