Gene expression changes in mouse forebrain deficient in Dnmt1 and Dnmt3a

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. 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.