DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation.

ABSTRACT: DNA methylation is a major epigenetic factor regulating genome reprogramming, cell differentiation and developmental gene expression. To understand the role of DNA methylation in central nervous system (CNS) neurons, we generated conditional Dnmt1 mutant mice that possess approximately 90% hypomethylated cortical and hippocampal cells in the dorsal forebrain from E13.5 on. The mutant mice were viable with a normal lifespan, but displayed severe neuronal cell death between E14.5 and three weeks postnatally. Accompanied with the striking cortical and hippocampal degeneration, adult mutant mice exhibited neurobehavioral defects in learning and memory in adulthood. Unexpectedly, a fraction of Dnmt1(-/-) cortical neurons survived throughout postnatal development, so that the residual cortex in

SUBMITTER: Hutnick LK 

PROVIDER: S-EPMC2706688 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature