Effects of cerebral ischemia in mice lacking DNA methyltransferase I in post-mitotic neurons

DNA methylation is important for controlling gene expression and is catalyzed by DNA methyltransferase (DnmtI) an enzyme abundant in brain. We recently demonstrated that, mice expressing reduced levels of DnmtI are protected from cerebral ischemia. Here, we used the cre/IoxP system to produce conditional mutants that lack Dnmt I in postmitotic neurons of the postnatal brain. We demonstrate that animals heterozygous for the conditional allele (DnmtI(llox/+)) have significantly smaller infarcts following Ih middle cerebral artery occlusion/reperfusion compared to their wildtype litters. Surprisingly, mice with a deletion of DnmtI in post-mitotic neurons (DnmtI(llox/c)) were not protected. In conclusion, we demonstrate that reduced levels of DnmtI, but not its absence, in post-mitotic neurons protect from ischemic brain injury. NeuroReport 12:3763-3766 (C) 2001 Lippincott Williams & Wilkins.