Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine Federico II, Edificio 18, Via Pansini 5, 80131 Naples, Italy.
Neurosci Lett. 2011 Oct 10;503(3):176-80. doi: 10.1016/j.neulet.2011.08.025. Epub 2011 Aug 22.
Tottering (tg) mice carry a missense mutation in the gene coding for P/Q-type voltage-dependent Ca(2+) channels (VDCCs). Aberrant functioning of P/Q-type VDCCs results in molecular alterations in Ca(2+) currents and in glutamate and dopamine systems. As a consequence, tottering mice exhibit mild ataxia, spontaneous epilepsy, and paroxysmal dyskinesia. In this study, we evaluated whether the tottering mice genotype (homozygous vs. heterozygous) and abnormal movement phenotype (mice exhibiting paroxysmal dyskinesia vs. mice not exhibiting dyskinesia) may affect the expression of Homer1a. Homer1a is a gene whose expression is modulated by glutamate, dopamine and Ca(2+) concentrations. Over-expression of Homer1a has been described in epilepsy and motor dysfunctions. Thereby, changes in Homer1a expression could take place in tottering mice. Studying the expression profile of this gene may shed light on the molecular events occurring in tottering mice. Moreover, tottering mice may represent a valuable animal model for investigating Homer1a involvement in motor disorders. Homer1a expression was decreased in all striatal subregions, with the exclusion of the dorsolateral caudate-putamen, in heterozygous mice compared to wild-type and homozygous mice. Gene expression was decreased in the core of the accumbens in mice exhibiting paroxysmal dyskinesia compared to wild-type mice and to mice not exhibiting dyskinesia. These results demonstrate that the tottering mouse genotype may affect striatal expression of Homer1a, possibly as a result of imbalance between Ca(2+) channels subtypes or Ca(2+)-related molecules in heterozygous vs. homozygous mice.
颤抖（tg）小鼠携带编码 P/Q 型电压依赖性钙（Ca2+）通道（VDCC）的基因突变。P/Q 型 VDCC 的异常功能导致 Ca2+电流和谷氨酸和多巴胺系统的分子改变。因此，颤抖小鼠表现出轻度共济失调、自发性癫痫和阵发性运动障碍。在这项研究中，我们评估了颤抖小鼠的基因型（纯合子与杂合子）和异常运动表型（表现阵发性运动障碍的小鼠与不表现运动障碍的小鼠）是否会影响 Homer1a 的表达。 Homer1a 是一种受谷氨酸、多巴胺和 Ca2+浓度调节的基因。 Homer1a 的过表达已在癫痫和运动功能障碍中得到描述。因此，颤抖小鼠中可能会发生 Homer1a 表达的变化。研究该基因的表达谱可能有助于了解颤抖小鼠中发生的分子事件。此外，颤抖小鼠可能代表研究 Homer1a 在运动障碍中的作用的有价值的动物模型。与野生型和纯合子小鼠相比，杂合子小鼠的所有纹状体亚区（除了外侧尾壳核）的 Homer1a 表达均降低。与野生型小鼠和不表现运动障碍的小鼠相比，表现阵发性运动障碍的小鼠的伏隔核核心的基因表达降低。这些结果表明，颤抖小鼠的基因型可能会影响 Homer1a 在纹状体中的表达，可能是由于杂合子与纯合子小鼠之间 Ca2+通道亚型或与 Ca2+相关的分子之间失衡所致。
