Takahashi Eiki, Niimi Kimie, Itakura Chitoshi
Research Resources Center, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Brain Res. 2009 Jul 7;1279:50-7. doi: 10.1016/j.brainres.2009.05.016. Epub 2009 May 13.
Although rolling Nagoya mice exhibit ataxia and carry a mutation in the alpha1 subunit of the Cav2.1 channel regulating neurotransmitter release, heterozygous mice have not received a great deal of attention. Given the pivotal role of Cav2.1 channels in controlling neurotransmitter release, age-dependent alterations in Cav2.1 channel function may result in aberrant synaptic signaling, leading to motor dysfunction. To examine age-related motor alterations in heterozygous mice, we used a battery of tests (e.g., motor activity, footprint, traction, wire suspension, balance beam, rotating rod, hind-limb extension analysis) in 2- and 22-month-old mice and examined expression patterns of the alpha1 gene in their cerebellum. No significant difference was observed between 2-month-old heterozygous and wild-type mice in the any of the behavioral tests or in the alpha1 expression levels. Although 22-month-old heterozygous and wild-type mice exhibited no significant difference in motor activity, footprint, or traction tests, 22-month-old heterozygous mice showed deficits in the wire hanging, balance beam, and rotating rod tests. Additionally, 22-month-old heterozygous mice displayed clasping behavior in the hind-limb extension test. Expression analysis showed that wild-type Cav2.1alpha(1) mRNA was lower in aged mice than in young mice and that mutant-type Cav2.1alpha(1) mRNA was higher in aged mice than in young mice. These findings suggest that heterozygous mice show age-related motor changes due to mutant-type Cav2.1 and that heterozygous mice may represent a new model for examining motor function.
尽管滚动名古屋小鼠表现出共济失调，并且在调节神经递质释放的Cav2.1通道的α1亚基中携带突变，但杂合子小鼠并未受到太多关注。鉴于Cav2.1通道在控制神经递质释放中的关键作用，Cav2.1通道功能的年龄依赖性改变可能导致异常的突触信号传导，从而导致运动功能障碍。为了研究杂合子小鼠与年龄相关的运动改变，我们对2个月和22个月大的小鼠进行了一系列测试（例如，运动活动、足迹、牵引力、悬线、平衡木、转棒、后肢伸展分析），并检查了它们小脑中α1基因的表达模式。在任何行为测试或α1表达水平上，2个月大的杂合子小鼠和野生型小鼠之间均未观察到显著差异。尽管22个月大的杂合子小鼠和野生型小鼠在运动活动、足迹或牵引力测试中没有显著差异，但22个月大的杂合子小鼠在悬线、平衡木和转棒测试中表现出缺陷。此外，22个月大的杂合子小鼠在后肢伸展测试中表现出紧握行为。表达分析表明，野生型Cav2.1α(1) mRNA在老年小鼠中低于年轻小鼠，而突变型Cav2.1α(1) mRNA在老年小鼠中高于年轻小鼠。这些发现表明，杂合子小鼠由于突变型Cav2.1而表现出与年龄相关的运动变化，并且杂合子小鼠可能代表一种用于研究运动功能的新模型。
