Early behavioral deficits in R6/2 mice suitable for use in preclinical drug testing
Early behavioral deficits in R6/2 mice suitable for use in preclinical drug testing
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DOI：
10.1016/j.nbd.2005.01.024
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发表时间：
2005-10-01
影响因子：
6.1
通讯作者：
Chesselet, MF
中科院分区：
文献类型：
--
作者：
Hickey, MA;Gallant, K;Chesselet, MF
亨廷顿氏病（HD）是由亨廷顿蛋白中延长的谷氨酰胺重复序列引起的神经退行性疾病。对突变的分子效应的进一步理解为治疗开辟了新的途径。高通量自动化行为测试产生明确的疾病进展标志物是体内药物筛选所必需的。我们已经在HD小鼠模型中确定了适合于成本有效的自动化分析的运动功能测试中的早期行为缺陷。R6/2 HD转基因小鼠的跑轮活动和攀爬行为早在4.5周龄时就减少了，当时转棒性能和握力仍然正常。功效计算表明，转轮试验适用于在如此早期进行高效、高通量的药物筛选。此外，这些数据扩大了在1个月大的R6/2小鼠中观察到的行为缺陷的范围，在这个年龄，已经可以在纹状体中检测到突触功能障碍。(c)2005年爱思唯尔公司All rights reserved.
Huntington's disease (HD) is a neurodegenerative disorder caused by an elongated glutamine repeat in huntingtin. Improved understanding of the molecular effects of the mutation opens new avenues for treatment. High-throughput automated behavioral tests that produce well-defined markers of disease progression are necessary for in vivo drug screening. We have identified early behavioral deficits in tests of motor function that are amenable to cost effective automated analysis in a mouse model of HD. Running wheel activity and climbing behavior were reduced in R6/2 HD transgenics from as early as 4.5 weeks of age, at a time when rotarod performance and grip strength were still normal. Power calculations showed that the running wheel test was appropriate for efficient, high-throughput drug screening at this early age. Furthermore, the data extend the range of behavioral deficits observed in I-month-old R6/2 mice, an age when synaptic dysfunction can already be detected in the striatum. (c) 2005 Elsevier Inc. All rights reserved.