Gene expression changes in mouse forebrain deficient in Dnmt1 and Dnmt3a. Mus musculus

Two major DNA methylation-catalyzing enzymes, Dnmt1 and Dnmt3a, are expressed in postmitotic neurons, but their function in the adult central nervous system is unclear. We generated conditional mutant mice (CamKIIa Cre; Dnmt loxP) that lack either Dnmt1 or Dnmt3a, or both, exclusively in forebrain excitatory neurons and found only double-knockout (DKO) mice exhibited abnormal hippocampal CA1 long-term plasticity and deficits of learning and memory. DKO neurons also exhibit a significant up-regulation of immune genes, such as class I MHC and Stat1, which are implicated in synaptic plasticity. Overall design: Four pairs of 2-3 month-old DKO and litter mate control were used. RNA samples were extracted from the cortex and hippocampus for gene expression array analysis.

两类核心DNA甲基化催化酶——DNA甲基转移酶1（Dnmt1）与DNA甲基转移酶3a（Dnmt3a）——在有丝分裂后神经元中表达，但其在成年中枢神经系统中的功能仍未明确。我们构建了仅在前脑兴奋性神经元中缺失DNA甲基转移酶1（Dnmt1）、DNA甲基转移酶3a（Dnmt3a）或同时缺失二者的条件性敲除小鼠（CamKIIa Cre; Dnmt loxP），仅双基因敲除（DKO）小鼠表现出海马CA1区长时程可塑性异常以及学习记忆功能缺陷。双基因敲除神经元还出现免疫基因的显著上调，包括与突触可塑性密切相关的主要组织相容性复合体I类（MHC I类）以及信号转导与转录激活因子1（Stat1）。实验设计概述：本研究使用4对2-3月龄的双基因敲除小鼠及其同窝对照小鼠，从皮层与海马组织中提取RNA样本，开展基因表达芯片分析。