アクチン結合タンパク質ドレブリンA欠損マウスにおける樹状突起スパインの形態形成と学習行動の解析

抄録

Drebrin A is a neuron-specific actin-binding protein, which is localized in mature dendritic spines. During synapse formation, embryonic isoform, drebrin E is converted into neuron-specific isoform, drebrin A. We have demonstrated that suppression of the upregulation of drebrin A attenuated spine formation in vitro. To investigate physiological differences of drebrins E and A, we generated mice, in which isoform conversion of drebrin did not occur, by targeted disruption of drebrin A specific exon (DAKO). In these mice total amount of drebrin was not changed since drebrin E was overexpressed instead of drebrin A. We first analyzed their dendritic spine morphology on apical dendrites of layer V pyramidal cells in somatosensory cortex using rapid Golgi staining. The number and length of dendritic spine in adult DAKO mice (16-18 week old) were comparable to that in wild-type mice. We next analyzed behavioral phenotypes in DAKO mice. These mice showed impaired context-dependent fear conditioning, a hippocampal NMDA receptor-dependent learning task. Our findings indicate that isoform conversion of drebrin is required for regulation of synaptic function. In contrast, total amount of drebrin is important for regulation of spine morphology. [J Physiol Sci. 2006;56 Suppl:S84]