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Abstract：
Progressive myoclonus epilepsy type 1 (EPM1) is an autosomal recessively inherited childhood-adolescence onset neurodegenerative disease caused by mutations in the cystatin B (CSTB gene). The key clinical manifestation in EPM1 is progressive, stimulus-sensitive, in particular action-induced myoclonus. The cystatin B-deficient mouse model, Cstb-/-, has been described to present with myoclonic seizures and progressive ataxia. Here we describe results from in-depth behavioral phenotyping of the Cstb-/- mouse model in pure isogenic 129S2/SvHsd background covering ages from 1.5 to 6 months. We developed a method for software-assisted detection of myoclonus from video recordings of the Cstb-/- mice. Additionally, we observed that the mice were hyperactive and showed reduced startle response, problems in motor coordination and lack of inhibition. We were, however, not able to demonstrate an ataxic phenotype in them. This detailed behavioral phenotyping of the Cstb-/- mice reveals new aspects of this mouse model. The nature of the motor problems in the Cstb-/- mice seems to be more complex and more resembling the human phenotype than initially described.
摘要：
进行性肌阵挛性癫痫1型（EPM1）是一种常染色体隐性遗传的儿童-青春期发作的神经退行性疾病，由胱抑素B（CSTB基因）突变引起。EPM1的主要临床表现是进行性，刺激敏感,特别是作用诱导的肌阵鸣。胱抑素B缺陷小鼠模型,Cstb-/-,已被描述为表现为肌阵挛性癫痫和进行性共济失调。在这里，我们描述了在纯等基因129S2/SvHsd背景下Cstb-/-小鼠模型的深入行为表型分析的结果，涵盖了1.5至6个月的年龄。我们开发了一种从Cstb-/-小鼠的视频记录中软件辅助检测肌阵鸣的方法。此外,我们观察到小鼠过度活跃，表现出减少的惊吓反应，运动协调问题和缺乏抑制作用。我们曾经,然而,不能证明他们共济失调的表型。Cstb-/-小鼠的这种详细的行为表型分析揭示了这种小鼠模型的新方面。Cstb-/-小鼠的运动问题的性质似乎比最初描述的更复杂并且更类似于人类表型。
