Elucidation of mechanisms for spontaneous epileptic seizures in mice lacking μ3B, a subunit of the neuron-specific AP-3B complex

接头蛋白（AP）复合物在后期分泌和内吞途径中调节货物蛋白的囊泡运输。μ3B是神经元特异性AP-3B复合物的一个亚基，缺乏μ3B的小鼠在15周龄后出现自发性癫痫发作。2003年，我们对μ3B敲除小鼠（KO）和野生型小鼠（WT）在2、4、6、8和16周龄时的CA1区域进行了形态计量学检测。常规组织学检查未见KO异常。2、4、6、8、16周龄时，KO大鼠突触钮扣大小与WT大鼠无显著差异，但KO大鼠抑制末端突触囊泡直径小于WT大鼠。4、6、8周龄时，KO大鼠兴奋性末梢突触囊泡直径小于WT大鼠，但2、16周龄时差异不显著。2004年，我们对μ3B敲除小鼠（KO）和野生型小鼠（WT）在2、4、6、8和16周龄时的CA3区进行了形态学检测。常规组织学检查未见KO异常。在4、6、8、16周龄时，KO和WT的突触钮扣大小没有差异，但在2周龄时，KO的抑制末端突触囊泡直径小于WT， KO的突触囊泡直径小于WT。另一方面，2-16周龄时，KO的苔藓纤维末梢突触囊泡直径大于WT。KO患者苔藓纤维末端的突触囊泡密度低于wt患者，而抑制性神经元末端的突触囊泡密度不低于wt患者。在该模型中，海马兴奋性和抑制性输入之间的不平衡可能引起癫痫发作。

Adaptor protein (AP) complexes regulate the vesicular transport of cargo proteins in the late secretory and endocytic pathways. Mice lacking μ3B, a subunit of the neuron-specific AP-3B complex, suffered from spontaneous epileptic seizures after the age of 15 weeks.In 2003, we performed morphometrical examinations of the CA1 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 2,4,6,8 and 16 weeks. The diameter of synaptic vesicles in excitatory terminals in KO was smaller than that in WT at the ages of 4,6 and 8 weeks, but not at the ages of 2 and 16 weeks. The densities of synaptic vesicles in both terminals in KO were lower than those in WT.In 2004, we performed morphometrical examinations of the CA3 region in μ3B knockout mice (KO) and wild type mice (WT) at the ages of 2,4,6,8 and 16 weeks. Conventional histological examinations revealed no abnormality in KO. There was no difference in the sizes of synaptic boutons between KO and WT. However, the diameter of synaptic vesicles in inhibitory terminals in KO was smaller than that in WT at the ages of 4,6,8 and 16 weeks, but not at the age of 2 weeks. On the other, the diameter of synaptic vesicles in mossy fiber terminals in KO was larger than that in WT at the ages of 2-16 weeks. The densities of synaptic vesicles in the mossy fiber terminals, but not the inhibitory, in KO were lower than those in WT.It is possible that the imbalance between excitatory and inhibitory inputs to the hippocampus evokes epileptic seizures in this model.