Adachi Megumi, Autry Anita E, Covington Herb E, Monteggia Lisa M
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
J Neurosci. 2009 Apr 1;29(13):4218-27. doi: 10.1523/JNEUROSCI.4225-08.2009.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that results from loss of function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Using viral-mediated basolateral amygdala (BLA)-specific deletion of Mecp2 in mice, we show that intact Mecp2 function is required for normal anxiety behavior as well as some types of learning and memory. To examine whether these behavioral deficits are the result of impaired transcriptional repression, because Mecp2 is believed to act as a transcriptional repressor in complex with histone deacetylases (HDACs), we infused a HDAC inhibitor chronically into the BLA of wild-type mice. We found that HDAC inhibition produces behavioral deficits similar to those observed after the deletion of Mecp2 in the BLA. These results suggest a key role for Mecp2 as a transcriptional repressor in the BLA in mediating behavioral features of RTT.
雷特综合征（RTT）是一种X连锁神经发育障碍，由甲基CpG结合蛋白2（MECP2）基因的功能丧失突变引起。利用病毒介导的在小鼠基底外侧杏仁核（BLA）中特异性缺失Mecp2，我们发现正常的焦虑行为以及某些类型的学习和记忆需要完整的Mecp2功能。为了研究这些行为缺陷是否是转录抑制受损的结果，因为Mecp2被认为与组蛋白脱乙酰酶（HDAC）形成复合物发挥转录抑制作用，我们将HDAC抑制剂长期注入野生型小鼠的BLA。我们发现HDAC抑制产生的行为缺陷与在BLA中缺失Mecp2后观察到的相似。这些结果表明Mecp2作为BLA中的转录抑制因子在介导RTT的行为特征中起关键作用。
