Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation
Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation
复制标题
DOI：
10.1523/jneurosci.16-09-03104.1996
复制
发表时间：
1996-05-01
影响因子：
5.3
通讯作者：
Wilson, MC
中科院分区：
文献类型：
--
作者：
Hess, EJ;Collins, KA;Wilson, MC
尽管运动过度在多种神经系统疾病中都有表达，但这种表型的生物学基础尚不清楚。小鼠突变型缺损 (Cm/+) 表现出由缺失突变引起的严重自发运动亢进。这种缺失涉及多个基因，其中包括编码 SNAP-25 的 Snap 基因，SNAP-25 是一种参与神经递质释放的神经末梢蛋白。给予苯丙胺（一种作用于突触前的药物）显着降低了缺损小鼠的运动活性，但增加了对照小鼠的活动，这表明突触前功能与行为异常有关。相比之下，精神兴奋剂哌甲酯增加了缺损小鼠和对照小鼠的运动活动。当编码 SNAP-25 的转基因被培育到缺损品系中以补充 Snap 缺失时，这些小鼠表达的过度活跃得到了挽救，使这些经过纠正的小鼠恢复到正常的运动活动水平。这些结果表明，这些小鼠表现出的过度活跃是突触前功能异常的结果，具体可归因于 SNAP-25 表达的缺陷。
Although hyperkinesis is expressed in several neurological disorders, the biological basis of this phenotype is unknown. The mouse mutant coloboma (Cm/+) exhibits profound spontaneous locomotor hyperactivity resulting from a deletion mutation. This deletion encompasses several genes including Snap, which encodes SNAP-25, a nerve terminal protein involved in neurotransmitter release. Administration of amphetamine, a drug that acts presynaptically, markedly reduced the locomotor activity in coloboma mice but increased the activity of control mice implicating presynaptic function in the behavioral abnormality. In contrast, the psychostimulant methylphenidate increased locomotor activity in both coloboma and control mice. When a transgene encoding SNAP-25 was bred into the coloboma strain to complement the Snap deletion, the hyperactivity expressed by these mice was rescued, returning these corrected mice to normal levels of locomotor activity. These results demonstrate that the hyperactivity exhibited by these mice is the result of abnormalities in presynaptic function specifically attributable to deficits in SNAP-25 expression.