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

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