Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function

Xinyu Zhao, Tetsuya Ueba, Brian R. Christie, Basam Barkho, Michael J. McConnell, Kinichi Nakashima, Edward S. Lein, Brennan D. Eadie, Andrew R. Willhoite, Alysson R. Muotri, Robert G. Summers, Jerold Chun, Kuo Fen Lee, Fred H. Gage

Research output: Contribution to journalArticlepeer-review

296 Citations (Scopus)

Abstract

DNA methylation-mediated epigenetic regulation plays critical roles in regulating mammalian gene expression, but its role in normal brain function is not clear. Methyl-CpG binding protein 1 (MBD1), a member of the methylated DNA-binding protein family, has been shown to bind methylated gene promoters and facilitate transcriptional repression in vitro. Here we report the generation and analysis of MBD1-/- mice. MBD1-/- mice had no detectable developmental defects and appeared healthy throughout life. However, we found that MBD1-/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability. Furthermore, adult MBD1-/- mice had decreased neurogenesis, impaired spatial learning, and a significant reduction in long-term potentiation in the dentate gyrus of the hippocampus. Our findings indicate that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions.

Original languageEnglish
Pages (from-to)6777-6782
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number11
DOIs
Publication statusPublished - May 27 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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