Hess E J, Collins K A, Wilson M C
Department of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, Hershey Medical Center, 17033, USA.
J Neurosci. 1996 May 1;16(9):3104-11. doi: 10.1523/JNEUROSCI.16-09-03104.1996.
Although hyperkinesis is expressed in several neurological disorders, the biological basis of this phenotype is unknown. The mouse mutant coloboma (Cml+) 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.
尽管运动亢进在多种神经系统疾病中都有表现，但其表型的生物学基础尚不清楚。小鼠突变体无虹膜（Cml+）由于缺失突变而表现出严重的自发运动亢进。该缺失包含多个基因，包括Snap，它编码SNAP-25，一种参与神经递质释放的神经末梢蛋白。苯丙胺是一种作用于突触前的药物，给予苯丙胺后，无虹膜小鼠的运动活性显著降低，但增加了对照小鼠的活性，这表明突触前功能与行为异常有关。相比之下，精神兴奋剂哌醋甲酯增加了无虹膜小鼠和对照小鼠的运动活性。当将编码SNAP-25的转基因培育到无虹膜品系中以补充Snap缺失时，这些小鼠表现出的多动得到了挽救，使这些纠正后的小鼠恢复到正常的运动活性水平。这些结果表明，这些小鼠表现出的多动是突触前功能异常的结果，具体归因于SNAP-25表达的缺陷。
